NM_001142308.3:c.695-6890G>T

Variant names:

• chr10-19116602-G-T
• rs16918253
• NM_001142308.3:c.695-6890G>T

Variant summary

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

The NM_001142308.3(MALRD1):​c.695-6890G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 152,098 control chromosomes in the GnomAD database, including 447 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 0.070 (447 hom., cov: 32)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALRD1	NM_001142308.3	c.695-6890G>T		intron_variant	Intron 5 of 39	ENST00000454679.7	NP_001135780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALRD1	ENST00000454679.7	c.695-6890G>T		intron_variant	Intron 5 of 39	1	NM_001142308.3	ENSP00000412763.3

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10628 AN: 151980 Hom.: 446 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0502

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0699 AC: 10632 AN: 152098 Hom.: 447 Cov.: 32 AF XY: 0.0703 AC XY: 5232 AN XY: 74376

African (AFR) AF: 0.116 AC: 4827 AN: 41474

American (AMR) AF: 0.0501 AC: 766 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.00503 AC: 26 AN: 5166

South Asian (SAS) AF: 0.125 AC: 601 AN: 4806

European-Finnish (FIN) AF: 0.0337 AC: 357 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0547 AC: 3718 AN: 67990

Other (OTH) AF: 0.0536 AC: 113 AN: 2108

Alfa AF: 0.0588 Hom.: 1126

Bravo AF: 0.0712

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.6
DANN	Benign	0.31
PhyloP100		0.59

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: rs16918253; hg19: chr10-19405531;