Genetic Variant MERTK:c.1451-72G>T (chr2-111997251-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 7922 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65823 hom. )

Consequence

MERTK
NM_006343.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.492

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3 link	c.1451-72G>T		intron_variant	Intron 9 of 18	ENST00000295408.9	NP_006334.2	Q12866

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MERTK	ENST00000295408.9 link	c.1451-72G>T	intron_variant	Intron 9 of 18	1	NM_006343.3	ENSP00000295408.4	Q12866
MERTK	ENST00000439966.5 link	n.*924-72G>T	intron_variant	Intron 9 of 18	1		ENSP00000402129.1	E9PD22
MERTK	ENST00000409780.5 link	c.923-72G>T	intron_variant	Intron 8 of 17	5		ENSP00000387277.1	E9PHX8
MERTK	ENST00000473065.1 link	n.-119G>T	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47969

AN:

151820

Hom.:

7906

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.323

AC:

81098

AN:

251064

Hom.:

14392

AF XY:

0.319

AC XY:

43362

AN XY:

135780

show subpopulations

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 SAS exome

AF:

0.358

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.:

AF XY:

0.304

AC XY:

207928

AN XY:

682950

show subpopulations

Gnomad4 AFR exome

AF:

0.338

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.316

AC:

48009

AN:

151938

Hom.:

7922

Cov.:

AF XY:

0.322

AC XY:

23901

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.353

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.452

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.279

Hom.:

8541

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

DANN

Benign

0.49

DEOGEN2

Benign

0.067

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.26

MetaRNN

Benign

0.00066

Sift4G

Uncertain

0.0060

Vest4

0.32

ClinPred

0.0073

GERP RS

-0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over