rs10508586

Variant names:

• chr10-19427560-C-T
• rs10508586
• NM_001142308.3:c.4846-22747C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142308.3(MALRD1):​c.4846-22747C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 152,142 control chromosomes in the GnomAD database, including 39 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 0.015 (39 hom., cov: 32)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0562 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.4846-22747C>T		intron	N/A	NP_001135780.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	ENST00000454679.7	TSL:1 MANE Select	c.4846-22747C>T		intron	N/A	ENSP00000412763.3
	MALRD1	ENST00000377266.7	TSL:5	c.2952+37951C>T		intron	N/A	ENSP00000366477.3

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 152024 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0612

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.00218

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00660

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0150 AC: 2275 AN: 152142 Hom.: 39 Cov.: 32 AF XY: 0.0150 AC XY: 1117 AN XY: 74376

African (AFR) AF: 0.0282 AC: 1170 AN: 41496

American (AMR) AF: 0.00465 AC: 71 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.0618 AC: 320 AN: 5182

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4818

European-Finnish (FIN) AF: 0.00218 AC: 23 AN: 10574

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00662 AC: 450 AN: 68004

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.0101 Hom.: 5

Bravo AF: 0.0159

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.60
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10508586; hg19: chr10-19716489;