rs799474

Positions:

• chr14-35046893-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM177A1	NM_173607.5	c.165+265C>G		intron_variant		ENST00000280987.9
FAM177A1	NM_001079519.1	c.96+265C>G		intron_variant
FAM177A1	NM_001289022.3	c.96+265C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM177A1	ENST00000280987.9	c.165+265C>G		intron_variant		1	NM_173607.5	A2

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

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.520

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

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.479

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
DANN	Benign	0.55

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: rs799474; hg19: chr14-35516099;