rs17670074

chr10-19416454-A-Cchr10-19416454-A-T

Variant summary

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

The NM_001142308.3(MALRD1):c.4845+26845A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,932 control chromosomes in the GnomAD database, including 25,538 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 0.54 (25538 hom., cov: 31)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALRD1	NM_001142308.3	c.4845+26845A>C		intron_variant		ENST00000454679.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALRD1	ENST00000454679.7	c.4845+26845A>C		intron_variant		1	NM_001142308.3	P1
MALRD1	ENST00000377266.7	c.2952+26845A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82133 AN: 151812 Hom.: 25478 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.541 AC: 82249 AN: 151932 Hom.: 25538 Cov.: 31 AF XY: 0.529 AC XY: 39308 AN XY: 74244

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.522

Alfa AF: 0.438 Hom.: 26480

Bravo AF: 0.565

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.85
Dann	Benign	0.73

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: rs17670074; hg19: chr10-19705383;