rs11884641

chr2-112009829-A-Gchr2-112009829-A-T

Variant summary

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

The NM_006343.3(MERTK):c.1961-119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 817,702 control chromosomes in the GnomAD database, including 30,071 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 0.25 (4981 hom., cov: 32)
  • Exomes 𝑓: 0.26 (25090 hom.)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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 = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MERTK	NM_006343.3	c.1961-119A>G		intron_variant		ENST00000295408.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MERTK	ENST00000295408.9	c.1961-119A>G		intron_variant		1	NM_006343.3	P1
MERTK	ENST00000439966.5	c.*1434-119A>G		intron_variant, NMD_transcript_variant		1
MERTK	ENST00000409780.5	c.1433-119A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37813 AN: 151722 Hom.: 4971 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.263 AC: 175109 AN: 665862 Hom.: 25090 AF XY: 0.264 AC XY: 95040 AN XY: 360296

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.249 AC: 37843 AN: 151840 Hom.: 4981 Cov.: 32 AF XY: 0.256 AC XY: 19010 AN XY: 74192

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.211

Alfa AF: 0.236 Hom.: 9175

Bravo AF: 0.240

Asia WGS AF: 0.208 AC: 726 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	0.13
Dann	Benign	0.33

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: rs11884641; hg19: chr2-112767406; COSMIC: COSV54930023;