NM_001142308.3:c.4846-24682G>A

Variant names:

• chr10-19425625-G-A
• rs12267418
• NM_001142308.3:c.4846-24682G>A

Variant summary

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

The NM_001142308.3(MALRD1):​c.4846-24682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,174 control chromosomes in the GnomAD database, including 3,571 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 0.18 (3571 hom., cov: 32)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142308.3. 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.4846-24682G>A		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.4846-24682G>A		intron	N/A	ENSP00000412763.3
	MALRD1	ENST00000377266.7	TSL:5	c.2952+36016G>A		intron	N/A	ENSP00000366477.3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26583 AN: 152056 Hom.: 3552 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.175 AC: 26651 AN: 152174 Hom.: 3571 Cov.: 32 AF XY: 0.169 AC XY: 12583 AN XY: 74422

African (AFR) AF: 0.376 AC: 15571 AN: 41466

American (AMR) AF: 0.120 AC: 1833 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3470

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5172

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4818

European-Finnish (FIN) AF: 0.0476 AC: 506 AN: 10620

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7548 AN: 68018

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.139 Hom.: 2546

Bravo AF: 0.192

Asia WGS AF: 0.0730 AC: 255 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.54
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12267418; hg19: chr10-19714554;