rs12476816

Variant names:

• chr2-61846962-G-A
• rs12476816
• NM_001201543.2:c.184-4602C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

FAM161A Gene-Disease associations (from GenCC):

• retinitis pigmentosa 28

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FAM161A	NM_001201543.2	c.184-4602C>T		intron_variant	Intron 1 of 6	ENST00000404929.6	NP_001188472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM161A	ENST00000404929.6	c.184-4602C>T		intron_variant	Intron 1 of 6	1	NM_001201543.2	ENSP00000385158.1

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

GnomAD2 exomes AF: 0.223 AC: 28559 AN: 128200 AF XY: 0.226

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 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

African (AFR) AF: 0.0452 AC: 383 AN: 8474

American (AMR) AF: 0.198 AC: 5301 AN: 26724

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 1842 AN: 10632

East Asian (EAS) AF: 0.313 AC: 2716 AN: 8688

South Asian (SAS) AF: 0.258 AC: 15219 AN: 59024

European-Finnish (FIN) AF: 0.274 AC: 3476 AN: 12688

Middle Eastern (MID) AF: 0.125 AC: 344 AN: 2752

European-Non Finnish (NFE) AF: 0.228 AC: 35875 AN: 157022

Other (OTH) AF: 0.227 AC: 3187 AN: 14066

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

African (AFR) AF: 0.0516 AC: 2114 AN: 41008

American (AMR) AF: 0.218 AC: 3296 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1644 AN: 5096

South Asian (SAS) AF: 0.293 AC: 1399 AN: 4778

European-Finnish (FIN) AF: 0.286 AC: 2988 AN: 10454

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15525 AN: 67838

Other (OTH) AF: 0.201 AC: 423 AN: 2100

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
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.27
PhyloP100		-1.5
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: rs12476816; hg19: chr2-62074097; COSMIC: COSV56765803;