rs9417254

Variant names:

• chr10-19727003-T-C
• rs9417254
• NM_001142308.3:c.6315-3703T>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.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
• Publications: 1 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]

ENSG00000233968 (HGNC:58180):

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 (AMR) allele frequency at 95% confidence interval = 0.455 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.6315-3703T>C		intron	N/A	NP_001135780.2
	MALRD1-AS1	NR_120646.1		n.146+1402A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	ENST00000454679.7	TSL:1 MANE Select	c.6315-3703T>C		intron	N/A	ENSP00000412763.3
	ENSG00000233968	ENST00000451713.5	TSL:1	n.146+1402A>G		intron	N/A
	ENSG00000233968	ENST00000657622.1		n.503A>G		non_coding_transcript_exon	Exon 1 of 3

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

African (AFR) AF: 0.141 AC: 5872 AN: 41554

American (AMR) AF: 0.464 AC: 7089 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1722 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2101 AN: 5166

South Asian (SAS) AF: 0.452 AC: 2177 AN: 4820

European-Finnish (FIN) AF: 0.450 AC: 4749 AN: 10562

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.452 AC: 30695 AN: 67968

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.419 Hom.: 44412

Bravo AF: 0.357

Asia WGS AF: 0.364 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.74
PhyloP100		0.22
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: rs9417254; hg19: chr10-20015932;