dbSNP rs799474: FAM177A1:c.165+265C>G (chr14-35046893-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173607.5(FAM177A1):c.165+265C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,271,432 control chromosomes in the GnomAD database, including 189,506 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 18102 hom., cov: 33)

Exomes 𝑓: 0.55 ( 171404 hom. )

Consequence

FAM177A1
NM_173607.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.185

Publications

9 publications found

Variant links:

Genes affected

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

FAM177A1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, G2P

FAM177A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FAM177A1	NM_173607.5 link	c.165+265C>G	intron_variant	Intron 1 of 4	ENST00000280987.9	NP_775878.2	Q8N128-2
FAM177A1	NM_001079519.1 link	c.96+265C>G	intron_variant	Intron 3 of 6		NP_001072987.1	Q8N128-1
FAM177A1	NM_001289022.3 link	c.96+265C>G	intron_variant	Intron 2 of 5		NP_001275951.1	Q8N128-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9 link	c.165+265C>G		intron_variant	Intron 1 of 4	1	NM_173607.5	ENSP00000280987.4		Q8N128-2

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

72075

AN:

152038

Hom.:

18108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.550

AC:

615660

AN:

1119276

Hom.:

171404

Cov.:

AF XY:

0.549

AC XY:

293456

AN XY:

534950

show subpopulations

African (AFR)

AF:

0.317

AC:

7199

AN:

22686

American (AMR)

AF:

0.354

AC:

2989

AN:

8452

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

7366

AN:

14880

East Asian (EAS)

AF:

0.426

AC:

9922

AN:

23296

South Asian (SAS)

AF:

0.442

AC:

18096

AN:

40956

European-Finnish (FIN)

AF:

0.630

AC:

13500

AN:

21436

Middle Eastern (MID)

AF:

0.451

AC:

1700

AN:

3768

European-Non Finnish (NFE)

AF:

0.566

AC:

531478

AN:

938786

Other (OTH)

AF:

0.520

AC:

23410

AN:

45016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

14574

29147

43721

58294

72868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16702

33404

50106

66808

83510

<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:

0.474

AC:

72094

AN:

152156

Hom.:

18102

Cov.:

AF XY:

0.474

AC XY:

35260

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.330

AC:

13707

AN:

41536

American (AMR)

AF:

0.388

AC:

5935

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.489

AC:

1697

AN:

3468

East Asian (EAS)

AF:

0.408

AC:

2107

AN:

5162

South Asian (SAS)

AF:

0.443

AC:

2141

AN:

4830

European-Finnish (FIN)

AF:

0.630

AC:

6660

AN:

10566

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.563

AC:

38253

AN:

67990

Other (OTH)

AF:

0.479

AC:

1011

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1912

3825

5737

7650

9562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.519

Hom.:

2639

Bravo

AF:

0.449

Asia WGS

AF:

0.406

AC:

1410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.8

(source)

DANN

Benign

0.55

PhyloP100

0.18

PromoterAI

-0.035

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over