Genetic Variant MALRD1:c.6137+29delT (chr10-19615941-AT-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+29delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 1015 hom., cov: 0)

Exomes 𝑓: 0.0096 ( 715 hom. )

Consequence

MALRD1
NM_001142308.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.149

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 (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALRD1	NM_001142308.3 link	c.6137+29delT		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+19delT	intron_variant	Intron 36 of 39	1	NM_001142308.3	ENSP00000412763.3	Q5VYJ5
MALRD1	ENST00000377266.7 link	c.4207+8040delT	intron_variant	Intron 22 of 24	5		ENSP00000366477.3	U5GXS0
MALRD1	ENST00000377265.3 link	c.1187+19delT	intron_variant	Intron 8 of 11	2		ENSP00000366476.3	H0Y3D6

Frequencies

GnomAD3 genomes

AF:

0.0651

AC:

9755

AN:

149846

Hom.:

1009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0145

Gnomad EAS

AF:

0.0361

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.00704

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.0518

GnomAD2 exomes

AF:

0.0247

AC:

2630

AN:

106568

AF XY:

0.0213

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.0446

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.0186

GnomAD4 exome

AF:

0.00965

AC:

12580

AN:

1303782

Hom.:

715

Cov.:

AF XY:

0.00921

AC XY:

5918

AN XY:

642520

show subpopulations

African (AFR)

AF:

0.225

AC:

6475

AN:

28810

American (AMR)

AF:

0.0162

AC:

511

AN:

31452

Ashkenazi Jewish (ASJ)

AF:

0.0151

AC:

348

AN:

23002

East Asian (EAS)

AF:

0.0277

AC:

924

AN:

33380

South Asian (SAS)

AF:

0.0170

AC:

1190

AN:

70106

European-Finnish (FIN)

AF:

0.0112

AC:

361

AN:

32266

Middle Eastern (MID)

AF:

0.0127

AC:

AN:

5350

European-Non Finnish (NFE)

AF:

0.00139

AC:

1430

AN:

1025156

Other (OTH)

AF:

0.0235

AC:

1273

AN:

54260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

448

896

1344

1792

2240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0653

AC:

9793

AN:

149952

Hom.:

1015

Cov.:

AF XY:

0.0645

AC XY:

4720

AN XY:

73158

show subpopulations

African (AFR)

AF:

0.216

AC:

8831

AN:

40890

American (AMR)

AF:

0.0230

AC:

345

AN:

15012

Ashkenazi Jewish (ASJ)

AF:

0.0145

AC:

AN:

3452

East Asian (EAS)

AF:

0.0362

AC:

183

AN:

5060

South Asian (SAS)

AF:

0.0208

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00704

AC:

AN:

10234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00134

AC:

AN:

67294

Other (OTH)

AF:

0.0595

AC:

123

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

378

756

1133

1511

1889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0128

Hom.:

1596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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10-19615941-AT-A

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