10-19165786-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001142308.3(MALRD1):c.1806G>A(p.Ala602=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 1,231,356 control chromosomes in the GnomAD database, including 2,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (291 hom., cov: 32)
  • Exomes 𝑓: 0.061 (2157 hom.)
• Consequence: MALRD1 NM_001142308.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00300

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-19165786-G-A is Benign according to our data. Variant chr10-19165786-G-A is described in ClinVar as [Benign]. Clinvar id is 769363.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.003 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALRD1	NM_001142308.3	c.1806G>A	p.Ala602=	synonymous_variant	13/40	ENST00000454679.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALRD1	ENST00000454679.7	c.1806G>A	p.Ala602=	synonymous_variant	13/40	1	NM_001142308.3	P1

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8792 AN: 151996 Hom.: 290 Cov.: 32

Gnomad AFR AF: 0.0688

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.0793

GnomAD4 exome AF: 0.0615 AC: 66333 AN: 1079242 Hom.: 2157 Cov.: 30 AF XY: 0.0613 AC XY: 31209 AN XY: 509438

Gnomad4 AFR exome AF: 0.0737

Gnomad4 AMR exome AF: 0.0574

Gnomad4 ASJ exome AF: 0.0897

Gnomad4 EAS exome AF: 0.0000754

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.0289

Gnomad4 NFE exome AF: 0.0642

Gnomad4 OTH exome AF: 0.0603

GnomAD4 genome AF: 0.0578 AC: 8792 AN: 152114 Hom.: 291 Cov.: 32 AF XY: 0.0552 AC XY: 4102 AN XY: 74352

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.0855

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0616

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0612 Hom.: 58

Bravo AF: 0.0620

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	3.7
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs78786296; hg19: chr10-19454715;