dbSNP rs4374383: MERTK:c.2079+3127A>G (chr2-112013193-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006343.3(MERTK):c.2079+3127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 153,820 control chromosomes in the GnomAD database, including 26,210 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 0.58 ( 25816 hom., cov: 29)

Exomes 𝑓: 0.61 ( 394 hom. )

Consequence

MERTK
NM_006343.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420

Publications

74 publications found

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 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

MERTK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3 link	c.2079+3127A>G		intron_variant	Intron 15 of 18	ENST00000295408.9	NP_006334.2	Q12866

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MERTK	ENST00000295408.9 link	c.2079+3127A>G	intron_variant	Intron 15 of 18	1	NM_006343.3	ENSP00000295408.4	Q12866
MERTK	ENST00000439966.5 link	n.*1552+3127A>G	intron_variant	Intron 15 of 18	1		ENSP00000402129.1	E9PD22
MERTK	ENST00000409780.5 link	c.1551+3127A>G	intron_variant	Intron 14 of 17	5		ENSP00000387277.1	E9PHX8

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87780

AN:

151646

Hom.:

25798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.596

GnomAD4 exome

AF:

0.612

AC:

1258

AN:

2056

Hom.:

394

Cov.:

AF XY:

0.598

AC XY:

614

AN XY:

1026

show subpopulations

African (AFR)

AF:

0.614

AC:

AN:

American (AMR)

AF:

0.750

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.670

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.613

AC:

928

AN:

1514

European-Non Finnish (NFE)

AF:

0.620

AC:

119

AN:

192

Other (OTH)

AF:

0.551

AC:

AN:

178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.579

AC:

87838

AN:

151764

Hom.:

25816

Cov.:

AF XY:

0.580

AC XY:

43013

AN XY:

74120

show subpopulations

African (AFR)

AF:

0.525

AC:

21689

AN:

41350

American (AMR)

AF:

0.598

AC:

9124

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

2263

AN:

3470

East Asian (EAS)

AF:

0.277

AC:

1420

AN:

5130

South Asian (SAS)

AF:

0.605

AC:

2891

AN:

4778

European-Finnish (FIN)

AF:

0.670

AC:

7052

AN:

10532

Middle Eastern (MID)

AF:

0.714

AC:

210

AN:

294

European-Non Finnish (NFE)

AF:

0.611

AC:

41505

AN:

67926

Other (OTH)

AF:

0.598

AC:

1262

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1800

3599

5399

7198

8998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.594

Hom.:

85588

Bravo

AF:

0.568

Asia WGS

AF:

0.469

AC:

1633

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.2

(source)

DANN

Benign

0.70

PhyloP100

-0.042

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over