rs799474

Variant names:

• chr14-35046893-C-G
• rs799474
• NM_173607.5:c.165+265C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 9 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173607.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM177A1	NM_173607.5	MANE Select	c.165+265C>G		intron	N/A	NP_775878.2	Q8N128-2
	FAM177A1	NM_001079519.1		c.96+265C>G		intron	N/A	NP_001072987.1	Q8N128-1
	FAM177A1	NM_001289022.3		c.96+265C>G		intron	N/A	NP_001275951.1	Q8N128-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM177A1	ENST00000280987.9	TSL:1 MANE Select	c.165+265C>G		intron	N/A	ENSP00000280987.4	Q8N128-2
	FAM177A1	ENST00000382406.7	TSL:1	c.96+265C>G		intron	N/A	ENSP00000371843.3	Q8N128-1
	FAM177A1	ENST00000555211.6	TSL:4	c.96+265C>G		intron	N/A	ENSP00000451508.2	Q8N128-1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72075 AN: 152038 Hom.: 18108 Cov.: 33

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.: 45 AF XY: 0.549 AC XY: 293456 AN XY: 534950

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

GnomAD4 genome AF: 0.474 AC: 72094 AN: 152156 Hom.: 18102 Cov.: 33 AF XY: 0.474 AC XY: 35260 AN XY: 74376

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.8
DANN	Benign	0.55
PhyloP100		0.18
PromoterAI		-0.035	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs799474; hg19: chr14-35516099;