rs9417254

Positions:

• chr10-19727003-T-C

Variant summary

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

The NM_001142308.3(MALRD1):​c.6315-3703T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,118 control chromosomes in the GnomAD database, including 11,808 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 0.37 (11808 hom., cov: 32)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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]

(HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MALRD1	NM_001142308.3	c.6315-3703T>C		intron_variant		ENST00000454679.7	NP_001135780.2
LOC101928834	NR_120646.1	n.146+1402A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MALRD1	ENST00000454679.7	c.6315-3703T>C		intron_variant		1	NM_001142308.3	ENSP00000412763	P1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55866 AN: 152000 Hom.: 11798 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.367 AC: 55873 AN: 152118 Hom.: 11808 Cov.: 32 AF XY: 0.371 AC XY: 27612 AN XY: 74366

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.371

Alfa AF: 0.434 Hom.: 30450

Bravo AF: 0.357

Asia WGS AF: 0.364 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.74

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: rs9417254; hg19: chr10-20015932;