rs7573344

chr2-111958740-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MERTK	NM_006343.3	c.758-6451A>G		intron_variant		ENST00000295408.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MERTK	ENST00000295408.9	c.758-6451A>G		intron_variant		1	NM_006343.3	P1
MERTK	ENST00000439966.5	c.*231-6451A>G		intron_variant, NMD_transcript_variant		1
MERTK	ENST00000409780.5	c.230-6451A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.0791

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.118

Alfa AF: 0.124 Hom.: 262

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

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: rs7573344; hg19: chr2-112716317;