Genetic Variant MALRD1:c.5321-8156G>C (chr10-19523038-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001142308.3(MALRD1):c.5321-8156G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 152,204 control chromosomes in the GnomAD database, including 180 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 0.036 ( 180 hom., cov: 32)

Consequence

MALRD1
NM_001142308.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285

Publications

0 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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new If you want to explore the variant's impact on the transcript NM_001142308.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142308.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	NM_001142308.3	MANE Select	c.5321-8156G>C		intron	N/A	NP_001135780.2	Q5VYJ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MALRD1	ENST00000454679.7	TSL:1 MANE Select	c.5321-8156G>C	intron	N/A	ENSP00000412763.3	Q5VYJ5
MALRD1	ENST00000377266.7	TSL:5	c.3458-8156G>C	intron	N/A	ENSP00000366477.3	U5GXS0
MALRD1	ENST00000377265.3	TSL:2	c.371-8156G>C	intron	N/A	ENSP00000366476.3	H0Y3D6

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5459

AN:

152086

Hom.:

177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.0568

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0360

AC:

5472

AN:

152204

Hom.:

180

Cov.:

AF XY:

0.0347

AC XY:

2584

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0908

AC:

3770

AN:

41524

American (AMR)

AF:

0.0116

AC:

177

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3470

East Asian (EAS)

AF:

0.0569

AC:

295

AN:

5182

South Asian (SAS)

AF:

0.0108

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0175

AC:

185

AN:

10598

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0127

AC:

863

AN:

68010

Other (OTH)

AF:

0.0257

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

263

525

788

1050

1313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.00918

Hom.:

Bravo

AF:

0.0399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.75

(source)

DANN

Benign

0.58

PhyloP100

-0.28

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over