chr2-61825245-A-G

Variant names:

• chr2-61825245-A-G
• rs3736598
• ENST00000456262.5:n.*2708T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 rank	MANE	Protein	UniProt
FAM161A	NM_001201543.2	c.*1210T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000404929.6	NP_001188472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM161A	ENST00000404929.6	c.*1210T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001201543.2	ENSP00000385158.1

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

GnomAD2 exomes AF: 0.421 AC: 51797 AN: 123000 AF XY: 0.414

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 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

African (AFR) AF: 0.359 AC: 2900 AN: 8068

American (AMR) AF: 0.540 AC: 13708 AN: 25368

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 2706 AN: 10432

East Asian (EAS) AF: 0.679 AC: 6291 AN: 9268

South Asian (SAS) AF: 0.445 AC: 24843 AN: 55886

European-Finnish (FIN) AF: 0.416 AC: 5093 AN: 12250

Middle Eastern (MID) AF: 0.221 AC: 249 AN: 1126

European-Non Finnish (NFE) AF: 0.341 AC: 53436 AN: 156568

Other (OTH) AF: 0.374 AC: 5101 AN: 13648

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

African (AFR) AF: 0.362 AC: 15036 AN: 41482

American (AMR) AF: 0.497 AC: 7598 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3533 AN: 5172

South Asian (SAS) AF: 0.478 AC: 2297 AN: 4810

European-Finnish (FIN) AF: 0.444 AC: 4672 AN: 10518

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22982 AN: 67974

Other (OTH) AF: 0.389 AC: 820 AN: 2110

Alfa AF: 0.346 Hom.: 8348

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Retinitis pigmentosa Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		1.4
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: rs3736598; hg19: chr2-62052380;