1-149791405-T-C

Position:

• chr1-149791405-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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. 14/19 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.282

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]

LOC124904411 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 1285171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-149791405-T-C is described in Lovd as [Likely_benign]. Variant chr1-149791405-T-C is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR1A	NM_000566.4	c.1013T>C	p.Ile338Thr	missense_variant	6/6	ENST00000369168.5	NP_000557.1
LOC124904411	XM_047438183.1	c.*576+553A>G		intron_variant			XP_047294139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR1A	ENST00000369168.5	c.1013T>C	p.Ile338Thr	missense_variant	6/6	1	NM_000566.4	ENSP00000358165	P1
	ENST00000428289.1	n.1063+553A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 523 AN: 146444 Hom.: 20 Cov.: 26

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

GnomAD3 exomes AF: 0.00418 AC: 1019 AN: 244050 Hom.: 102 AF XY: 0.00409 AC XY: 542 AN XY: 132610

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 SAS exome AF: 0.000365

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.: 31 AF XY: 0.00422 AC XY: 3051 AN XY: 722794

Gnomad4 AFR exome AF: 0.000908

Gnomad4 AMR exome AF: 0.00220

Gnomad4 ASJ exome AF: 0.00831

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000479

Gnomad4 FIN exome AF: 0.00899

Gnomad4 NFE exome AF: 0.00462

Gnomad4 OTH exome AF: 0.00458

GnomAD4 genome AF: 0.00357 AC: 523 AN: 146550 Hom.: 20 Cov.: 26 AF XY: 0.00322 AC XY: 231 AN XY: 71638

Gnomad4 AFR AF: 0.000989

Gnomad4 AMR AF: 0.00289

Gnomad4 ASJ AF: 0.00879

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00661

Gnomad4 NFE AF: 0.00504

Gnomad4 OTH AF: 0.00347

Alfa AF: 0.00448 Hom.: 9

Bravo AF: 0.00333

ESP6500AA AF: 0.000710 AC: 3

ESP6500EA AF: 0.00554 AC: 47

ExAC AF: 0.00433 AC: 510

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	FCGR1A: PP2, BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.17
DANN	Benign	0.66
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00035	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.6	N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.011
MVP		0.082
ClinPred		0.0014	T
GERP RS		-1.0
Varity_R		0.033
gMVP		0.028

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

LitVar

Other links and lift over

dbSNP: rs1050208; hg19: chr1-149762961;