chr10-19621609-T-C

Variant names:

• chr10-19621609-T-C
• rs10764094
• NM_001142308.3:c.6137+5686T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.91).
• 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 rank	MANE	Protein	UniProt
MALRD1	NM_001142308.3	c.6137+5686T>C		intron_variant	Intron 36 of 39	ENST00000454679.7	NP_001135780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALRD1	ENST00000454679.7	c.6137+5686T>C		intron_variant	Intron 36 of 39	1	NM_001142308.3	ENSP00000412763.3
MALRD1	ENST00000377266.7	c.4207+13707T>C		intron_variant	Intron 22 of 24	5		ENSP00000366477.3
MALRD1	ENST00000377265.3	c.1187+5686T>C		intron_variant	Intron 8 of 11	2		ENSP00000366476.3

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

African (AFR) AF: 0.175 AC: 7252 AN: 41446

American (AMR) AF: 0.359 AC: 5451 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1295 AN: 3464

East Asian (EAS) AF: 0.373 AC: 1917 AN: 5140

South Asian (SAS) AF: 0.308 AC: 1481 AN: 4816

European-Finnish (FIN) AF: 0.569 AC: 5933 AN: 10432

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.484 AC: 32704 AN: 67624

Other (OTH) AF: 0.364 AC: 762 AN: 2096

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
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs10764094; hg19: chr10-19910538;