rs10764094

chr10-19621609-T-Cchr10-19621609-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142308.3(MALRD1):c.6137+5686T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,414 control chromosomes in the GnomAD database, including 12,281 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 0.38 (12281 hom., cov: 32)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALRD1	NM_001142308.3	c.6137+5686T>C		intron_variant		ENST00000454679.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALRD1	ENST00000454679.7	c.6137+5686T>C		intron_variant		1	NM_001142308.3	P1
MALRD1	ENST00000377265.3	c.1188+5686T>C		intron_variant		2
MALRD1	ENST00000377266.7	c.4207+13707T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57328 AN: 151296 Hom.: 12283 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.379 AC: 57334 AN: 151414 Hom.: 12281 Cov.: 32 AF XY: 0.379 AC XY: 28024 AN XY: 73954

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.364

Alfa AF: 0.298 Hom.: 847

Bravo AF: 0.353

Asia WGS AF: 0.357 AC: 1234 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.0
Dann	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs10764094; hg19: chr10-19910538;