rs3811632

Variant names:

• chr2-111997251-G-T
• rs3811632
• NM_006343.3:c.1451-72G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-111997251-G-T
• chr2-111997251-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006343.3(MERTK):​c.1451-72G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,512,912 control chromosomes in the GnomAD database, including 73,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.32 (7922 hom., cov: 32)
  • Exomes 𝑓: 0.30 (65823 hom.)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492
• Publications: 18 publications found

Genes affected

MERTK (HGNC:7027): (MER proto-oncogene, tyrosine kinase) This gene is a member of the MER/AXL/TYRO3 receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. Mutations in this gene have been associated with disruption of the retinal pigment epithelium (RPE) phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (RP). [provided by RefSeq, Jul 2008]

MERTK Gene-Disease associations (from GenCC):

• MERTK-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 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 (MetaRNN=6.637871E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006343.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MERTK	NM_006343.3	MANE Select	c.1451-72G>T		intron	N/A	NP_006334.2	Q12866

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MERTK	ENST00000295408.9	TSL:1 MANE Select	c.1451-72G>T		intron	N/A	ENSP00000295408.4	Q12866
	MERTK	ENST00000439966.5	TSL:1	n.*924-72G>T		intron	N/A	ENSP00000402129.1	E9PD22
	MERTK	ENST00000953051.1		c.1451-72G>T		intron	N/A	ENSP00000623110.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47969 AN: 151820 Hom.: 7906 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.323 AC: 81098 AN: 251064 AF XY: 0.319

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.459

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.304 AC: 414291 AN: 1360974 Hom.: 65823 Cov.: 22 AF XY: 0.304 AC XY: 207928 AN XY: 682950

African (AFR) AF: 0.338 AC: 10636 AN: 31512

American (AMR) AF: 0.446 AC: 19885 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 6789 AN: 25546

East Asian (EAS) AF: 0.114 AC: 4480 AN: 39302

South Asian (SAS) AF: 0.356 AC: 30017 AN: 84278

European-Finnish (FIN) AF: 0.445 AC: 23690 AN: 53248

Middle Eastern (MID) AF: 0.250 AC: 1402 AN: 5604

European-Non Finnish (NFE) AF: 0.294 AC: 300122 AN: 1019818

Other (OTH) AF: 0.302 AC: 17270 AN: 57096

GnomAD4 genome AF: 0.316 AC: 48009 AN: 151938 Hom.: 7922 Cov.: 32 AF XY: 0.322 AC XY: 23901 AN XY: 74242

African (AFR) AF: 0.336 AC: 13916 AN: 41416

American (AMR) AF: 0.353 AC: 5397 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 952 AN: 3468

East Asian (EAS) AF: 0.105 AC: 544 AN: 5158

South Asian (SAS) AF: 0.348 AC: 1679 AN: 4822

European-Finnish (FIN) AF: 0.452 AC: 4751 AN: 10508

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19753 AN: 67960

Other (OTH) AF: 0.279 AC: 589 AN: 2110

Alfa AF: 0.283 Hom.: 12090

Bravo AF: 0.308

TwinsUK AF: 0.286 AC: 1061

ALSPAC AF: 0.292 AC: 1124

ESP6500AA AF: 0.345 AC: 604

ESP6500EA AF: 0.284 AC: 1132

ExAC AF: 0.319 AC: 38692

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.49
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.00066	T
PhyloP100		0.49
Sift4G	Uncertain	0.0060	D
Vest4		0.32
ClinPred		0.0073	T
GERP RS		-0.38
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: rs3811632; hg19: chr2-112754828; COSMIC: COSV54927100; COSMIC: COSV54927100;