chr1-149791405-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000566.4(FCGR1A):c.1013T>C(p.Ile338Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,599,558 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 20 hom., cov: 26)

Exomes 𝑓: 0.0043 ( 306 hom. )

Consequence

FCGR1A
NM_000566.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.282

Publications

5 publications found

Variant links:

Genes affected

FCGR1A (HGNC:3613): (Fc gamma receptor Ia) This gene encodes a protein that plays an important role in the immune response. This protein is a high-affinity Fc-gamma receptor. The gene is one of three related gene family members located on chromosome 1. [provided by RefSeq, Jul 2008]

FCGR1A links:

ENSG00000233030 (HGNC:):

ENSG00000233030 links:

H2BC18 (HGNC:24700): (H2B clustered histone 18) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-dependent histone that is a member of the histone H2B family and is found in a histone cluster on chromosome 1. [provided by RefSeq, Aug 2015]

H2BC18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051913857).

BP6

Variant 1-149791405-T-C is Benign according to our data. Variant chr1-149791405-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1285171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 20 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000566.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCGR1A	NM_000566.4	MANE Select	c.1013T>C	p.Ile338Thr	missense	Exon 6 of 6	NP_000557.1	P12314-1
FCGR1A	NM_001378804.1		c.1016T>C	p.Ile339Thr	missense	Exon 6 of 6	NP_001365733.1
FCGR1A	NM_001378805.1		c.992T>C	p.Ile331Thr	missense	Exon 5 of 5	NP_001365734.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCGR1A	ENST00000369168.5	TSL:1 MANE Select	c.1013T>C	p.Ile338Thr	missense	Exon 6 of 6	ENSP00000358165.4	P12314-1
ENSG00000233030	ENST00000428289.1	TSL:1	n.1063+553A>G		intron	N/A
FCGR1A	ENST00000964516.1		c.1103T>C	p.Ile368Thr	missense	Exon 7 of 7	ENSP00000634575.1

Frequencies

GnomAD3 genomes

AF:

0.00357

AC:

523

AN:

146444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000992

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00289

Gnomad ASJ

AF:

0.00879

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00504

Gnomad OTH

AF:

0.00351

GnomAD2 exomes

AF:

0.00418

AC:

1019

AN:

244050

AF XY:

0.00409

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00820

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00954

Gnomad NFE exome

AF:

0.00543

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00431

AC:

6264

AN:

1453008

Hom.:

306

Cov.:

AF XY:

0.00422

AC XY:

3051

AN XY:

722794

show subpopulations

African (AFR)

AF:

0.000908

AC:

AN:

33030

American (AMR)

AF:

0.00220

AC:

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.00831

AC:

214

AN:

25758

East Asian (EAS)

AF:

0.00

AC:

AN:

39238

South Asian (SAS)

AF:

0.000479

AC:

AN:

85538

European-Finnish (FIN)

AF:

0.00899

AC:

479

AN:

53278

Middle Eastern (MID)

AF:

0.00147

AC:

AN:

4086

European-Non Finnish (NFE)

AF:

0.00462

AC:

5122

AN:

1107792

Other (OTH)

AF:

0.00458

AC:

274

AN:

59784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

416

833

1249

1666

2082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00357

AC:

523

AN:

146550

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

231

AN XY:

71638

show subpopulations

African (AFR)

AF:

0.000989

AC:

AN:

38414

American (AMR)

AF:

0.00289

AC:

AN:

14892

Ashkenazi Jewish (ASJ)

AF:

0.00879

AC:

AN:

3298

East Asian (EAS)

AF:

0.000200

AC:

AN:

5002

South Asian (SAS)

AF:

0.00

AC:

AN:

4620

European-Finnish (FIN)

AF:

0.00661

AC:

AN:

10282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00504

AC:

337

AN:

66850

Other (OTH)

AF:

0.00347

AC:

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00448

Hom.:

Bravo

AF:

0.00333

ESP6500AA

AF:

0.000710

AC:

ESP6500EA

AF:

0.00554

AC:

ExAC

AF:

0.00433

AC:

510

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.17

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.051

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00035

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.6

PhyloP100

-0.28

PrimateAI

Benign

0.37

PROVEAN

Benign

0.96

REVEL

Benign

0.031

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.011

MVP

0.082

ClinPred

0.0014

GERP RS

-1.0

Varity_R

0.033

gMVP

0.028

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over