rs12477716

Positions:

• chr2-111911067-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006343.3(MERTK):​c.61+12271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,020 control chromosomes in the GnomAD database, including 4,709 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 0.24 (4709 hom., cov: 31)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MERTK	NM_006343.3	c.61+12271C>T		intron_variant		ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.61+12271C>T		intron_variant		1	NM_006343.3	ENSP00000295408	P1
MERTK	ENST00000439966.5	c.61+12271C>T		intron_variant, NMD_transcript_variant		1		ENSP00000402129
MERTK	ENST00000409780.5	c.-47+12271C>T		intron_variant		5		ENSP00000387277

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36349 AN: 151902 Hom.: 4701 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.239 AC: 36377 AN: 152020 Hom.: 4709 Cov.: 31 AF XY: 0.246 AC XY: 18292 AN XY: 74276

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.198

Alfa AF: 0.263 Hom.: 897

Bravo AF: 0.230

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.39

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: rs12477716; hg19: chr2-112668644;