Genetic Variant NM_001142308.3:c.6137+28_6137+29delTT (chr10-19615941-ATT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001142308.3(MALRD1):c.6137+28_6137+29delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,456,938 control chromosomes in the GnomAD database, including 194,852 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 15691 hom., cov: 0)

Exomes 𝑓: 0.53 ( 179161 hom. )

Consequence

MALRD1
NM_001142308.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.565

Publications

1 publications found

Variant links:

Genes affected

MALRD1 (HGNC:24331): (MAM and LDL receptor class A domain containing 1) This gene encodes a conserved protein that features multiple MAM (meprin-A5-protein tyrosine phosphatase mu) and LDLR A2 (low density lipoprotein receptor A2) domains. Expression of this gene is enriched in the small intestine and is upregulated during differentiation of a human cell line that exhibits properties of intestinal epithelial cells. The encoded protein has been shown to modulate production of FGF19 in a human intestinal cell line and may regulate bile acid metabolism in the liver. A synergistic interaction between an allele of this gene and the APOE E4 allele is associated with an elevated risk of Alzheimer's disease in human patients. [provided by RefSeq, Jul 2017]

MALRD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALRD1	NM_001142308.3 link	c.6137+28_6137+29delTT		intron_variant	Intron 36 of 39	ENST00000454679.7	NP_001135780.2	Q5VYJ5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MALRD1	ENST00000454679.7 link	c.6137+19_6137+20delTT	intron_variant	Intron 36 of 39	1	NM_001142308.3	ENSP00000412763.3	Q5VYJ5
MALRD1	ENST00000377266.7 link	c.4207+8040_4207+8041delTT	intron_variant	Intron 22 of 24	5		ENSP00000366477.3	U5GXS0
MALRD1	ENST00000377265.3 link	c.1187+19_1187+20delTT	intron_variant	Intron 8 of 11	2		ENSP00000366476.3	H0Y3D6

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

67819

AN:

149792

Hom.:

15689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.445

Gnomad NFE

AF:

0.530

Gnomad OTH

AF:

0.447

GnomAD2 exomes

AF:

0.547

AC:

58283

AN:

106568

AF XY:

0.552

show subpopulations

Gnomad AFR exome

AF:

0.381

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.521

Gnomad EAS exome

AF:

0.529

Gnomad FIN exome

AF:

0.610

Gnomad NFE exome

AF:

0.610

Gnomad OTH exome

AF:

0.575

GnomAD4 exome

AF:

0.529

AC:

691743

AN:

1307040

Hom.:

179161

AF XY:

0.526

AC XY:

339095

AN XY:

644260

show subpopulations

African (AFR)

AF:

0.334

AC:

9663

AN:

28944

American (AMR)

AF:

0.392

AC:

12434

AN:

31696

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

10517

AN:

23110

East Asian (EAS)

AF:

0.505

AC:

16944

AN:

33536

South Asian (SAS)

AF:

0.391

AC:

27656

AN:

70738

European-Finnish (FIN)

AF:

0.560

AC:

18114

AN:

32366

Middle Eastern (MID)

AF:

0.438

AC:

2348

AN:

5366

European-Non Finnish (NFE)

AF:

0.552

AC:

566750

AN:

1026880

Other (OTH)

AF:

0.502

AC:

27317

AN:

54404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

15262

30524

45786

61048

76310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.453

AC:

67847

AN:

149898

Hom.:

15691

Cov.:

AF XY:

0.449

AC XY:

32833

AN XY:

73126

show subpopulations

African (AFR)

AF:

0.327

AC:

13385

AN:

40902

American (AMR)

AF:

0.410

AC:

6143

AN:

14998

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

1487

AN:

3452

East Asian (EAS)

AF:

0.429

AC:

2166

AN:

5054

South Asian (SAS)

AF:

0.348

AC:

1659

AN:

4762

European-Finnish (FIN)

AF:

0.570

AC:

5826

AN:

10228

Middle Eastern (MID)

AF:

0.451

AC:

129

AN:

286

European-Non Finnish (NFE)

AF:

0.530

AC:

35647

AN:

67260

Other (OTH)

AF:

0.445

AC:

919

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1831

3663

5494

7326

9157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.402

Hom.:

1596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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NM_001142308.3:c.6137+28_6137+29delTT

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