rs12476816

Positions:

• chr2-61846962-G-A
• chr2-61846962-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201543.2(FAM161A):​c.184-4602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 451,152 control chromosomes in the GnomAD database, including 11,526 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 0.19 (3218 hom., cov: 32)
  • Exomes 𝑓: 0.23 (8308 hom.)
• Consequence: FAM161A NM_001201543.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

Genes affected

FAM161A (HGNC:25808): (FAM161 centrosomal protein A) This gene belongs to the FAM161 family. It is expressed mainly in the retina. Mouse studies suggested that this gene is involved in development of retinal progenitors during embryogenesis, and that its activity is restricted to mature photoreceptors after birth. Mutations in this gene cause autosomal recessive retinitis pigmentosa-28. Alternatively spliced transcript variants have been identified.[provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM161A	NM_001201543.2	c.184-4602C>T		intron_variant		ENST00000404929.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM161A	ENST00000404929.6	c.184-4602C>T		intron_variant		1	NM_001201543.2	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28169 AN: 150964 Hom.: 3220 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.197

GnomAD3 exomes AF: 0.223 AC: 28559 AN: 128200 Hom.: 3521 AF XY: 0.226 AC XY: 15814 AN XY: 69890

Gnomad AFR exome AF: 0.0416

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.322

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.228 AC: 68343 AN: 300070 Hom.: 8308 Cov.: 0 AF XY: 0.232 AC XY: 39675 AN XY: 171014

Gnomad4 AFR exome AF: 0.0452

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.186 AC: 28174 AN: 151082 Hom.: 3218 Cov.: 32 AF XY: 0.192 AC XY: 14159 AN XY: 73780

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.201

Alfa AF: 0.200 Hom.: 661

Bravo AF: 0.171

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.27

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: rs12476816; hg19: chr2-62074097; COSMIC: COSV56765803;