10-19712639-A-G

Variant names:

• chr10-19712639-A-G
• rs11011216
• NM_001142308.3:c.6315-18067A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001142308.3(MALRD1):​c.6315-18067A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 152,264 control chromosomes in the GnomAD database, including 753 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 0.090 (753 hom., cov: 32)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 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.6315-18067A>G		intron	N/A	NP_001135780.2
	MALRD1-AS1	NR_120646.1		n.444-1351T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	ENST00000454679.7	TSL:1 MANE Select	c.6315-18067A>G		intron	N/A	ENSP00000412763.3
	ENSG00000233968	ENST00000451713.5	TSL:1	n.444-1351T>C		intron	N/A
	MALRD1	ENST00000377266.7	TSL:5	c.4305-18067A>G		intron	N/A	ENSP00000366477.3

Frequencies

GnomAD3 genomes AF: 0.0899 AC: 13683 AN: 152146 Hom.: 750 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0396

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.0919

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

GnomAD4 genome AF: 0.0900 AC: 13700 AN: 152264 Hom.: 753 Cov.: 32 AF XY: 0.0867 AC XY: 6454 AN XY: 74466

African (AFR) AF: 0.151 AC: 6286 AN: 41532

American (AMR) AF: 0.0633 AC: 969 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3472

East Asian (EAS) AF: 0.0457 AC: 237 AN: 5186

South Asian (SAS) AF: 0.0722 AC: 349 AN: 4834

European-Finnish (FIN) AF: 0.0396 AC: 420 AN: 10614

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0730 AC: 4964 AN: 68010

Other (OTH) AF: 0.0909 AC: 192 AN: 2112

Alfa AF: 0.0830 Hom.: 77

Bravo AF: 0.0943

Asia WGS AF: 0.0570 AC: 199 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.72
PhyloP100		2.1
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: rs11011216; hg19: chr10-20001568;