10-19578702-G-T

Variant names:

• chr10-19578702-G-T
• rs10740923
• NM_001142308.3:c.5680+10999G>T

Variant summary

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

The ENST00000454679.7(MALRD1):​c.5680+10999G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 148,674 control chromosomes in the GnomAD database, including 19,206 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 0.51 (19206 hom., cov: 29)
• Consequence: MALRD1 ENST00000454679.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• 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 = 0.527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000454679.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	NM_001142308.3	MANE Select	c.5680+10999G>T		intron	N/A	NP_001135780.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	ENST00000454679.7	TSL:1 MANE Select	c.5680+10999G>T		intron	N/A	ENSP00000412763.3
	MALRD1	ENST00000377266.7	TSL:5	c.3817+10999G>T		intron	N/A	ENSP00000366477.3
	MALRD1	ENST00000377265.3	TSL:2	c.730+10999G>T		intron	N/A	ENSP00000366476.3

Frequencies

GnomAD3 genomes AF: 0.511 AC: 75862 AN: 148594 Hom.: 19200 Cov.: 29

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.511 AC: 75900 AN: 148674 Hom.: 19206 Cov.: 29 AF XY: 0.507 AC XY: 36708 AN XY: 72352

African (AFR) AF: 0.527 AC: 21397 AN: 40582

American (AMR) AF: 0.434 AC: 6454 AN: 14858

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1530 AN: 3430

East Asian (EAS) AF: 0.373 AC: 1873 AN: 5024

South Asian (SAS) AF: 0.393 AC: 1840 AN: 4676

European-Finnish (FIN) AF: 0.564 AC: 5513 AN: 9768

Middle Eastern (MID) AF: 0.462 AC: 134 AN: 290

European-Non Finnish (NFE) AF: 0.531 AC: 35656 AN: 67096

Other (OTH) AF: 0.488 AC: 1004 AN: 2056

Alfa AF: 0.514 Hom.: 25195

Bravo AF: 0.496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.37
PhyloP100		0.073
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10740923; hg19: chr10-19867631; COSMIC: COSV65980841;