rs7573344

Variant names:

• chr2-111958740-A-G
• rs7573344
• NM_006343.3:c.758-6451A>G

Variant summary

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

The NM_006343.3(MERTK):​c.758-6451A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,136 control chromosomes in the GnomAD database, including 1,144 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 0.11 (1144 hom., cov: 32)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 8 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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3	c.758-6451A>G		intron_variant	Intron 4 of 18	ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.758-6451A>G		intron_variant	Intron 4 of 18	1	NM_006343.3	ENSP00000295408.4
MERTK	ENST00000439966.5	n.*231-6451A>G		intron_variant	Intron 4 of 18	1		ENSP00000402129.1
MERTK	ENST00000409780.5	c.230-6451A>G		intron_variant	Intron 3 of 17	5		ENSP00000387277.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16251 AN: 152018 Hom.: 1145 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.0784

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.117

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.107 AC: 16254 AN: 152136 Hom.: 1144 Cov.: 32 AF XY: 0.106 AC XY: 7871 AN XY: 74368

African (AFR) AF: 0.0238 AC: 989 AN: 41522

American (AMR) AF: 0.107 AC: 1642 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3468

East Asian (EAS) AF: 0.244 AC: 1264 AN: 5170

South Asian (SAS) AF: 0.0791 AC: 381 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1464 AN: 10576

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.141 AC: 9605 AN: 67978

Other (OTH) AF: 0.118 AC: 250 AN: 2112

Alfa AF: 0.126 Hom.: 506

Bravo AF: 0.103

Asia WGS AF: 0.160 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		0.13
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: rs7573344; hg19: chr2-112716317;