chr2-61825245-A-G

Position:

• chr2-61825245-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001201543.2(FAM161A):​c.*1210T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 444,628 control chromosomes in the GnomAD database, including 35,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11701 hom., cov: 32)
  • Exomes 𝑓: 0.39 (23765 hom.)
• Consequence: FAM161A NM_001201543.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.41

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 2-61825245-A-G is Benign according to our data. Variant chr2-61825245-A-G is described in ClinVar as [Benign]. Clinvar id is 336715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM161A	NM_001201543.2	c.*1210T>C		3_prime_UTR_variant	7/7	ENST00000404929.6	NP_001188472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM161A	ENST00000404929.6	c.*1210T>C		3_prime_UTR_variant	7/7	1	NM_001201543.2	ENSP00000385158	P1
FAM161A	ENST00000405894.3	c.*1210T>C		3_prime_UTR_variant	6/6	1		ENSP00000385893
FAM161A	ENST00000456262.5	c.*2708T>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000396105
FAM161A	ENST00000418113.5	c.*1833T>C		3_prime_UTR_variant, NMD_transcript_variant	8/8	5		ENSP00000416861

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58060 AN: 151896 Hom.: 11671 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.383

GnomAD3 exomes AF: 0.421 AC: 51797 AN: 123000 Hom.: 11885 AF XY: 0.414 AC XY: 27665 AN XY: 66856

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.541

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.683

Gnomad SAS exome AF: 0.446

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.335

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.391 AC: 114327 AN: 292614 Hom.: 23765 Cov.: 0 AF XY: 0.393 AC XY: 65421 AN XY: 166506

Gnomad4 AFR exome AF: 0.359

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.679

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.416

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.382 AC: 58132 AN: 152014 Hom.: 11701 Cov.: 32 AF XY: 0.393 AC XY: 29206 AN XY: 74310

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.389

Alfa AF: 0.343 Hom.: 7025

Bravo AF: 0.385

Asia WGS AF: 0.586 AC: 2028 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	10
DANN	Benign	0.88

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: rs3736598; hg19: chr2-62052380;