rs10740923
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001142308.3(MALRD1):c.5680+10999G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000672 in 148,748 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 ( 0 hom., cov: 29)
Consequence
MALRD1
NM_001142308.3 intron
NM_001142308.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0730
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MALRD1 | NM_001142308.3 | c.5680+10999G>C | intron_variant | ENST00000454679.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MALRD1 | ENST00000454679.7 | c.5680+10999G>C | intron_variant | 1 | NM_001142308.3 | P1 | |||
MALRD1 | ENST00000377265.3 | c.731+10999G>C | intron_variant | 2 | |||||
MALRD1 | ENST00000377266.7 | c.3817+10999G>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000672 AC: 1AN: 148748Hom.: 0 Cov.: 29
GnomAD3 genomes
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00000672 AC: 1AN: 148748Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 1AN XY: 72334
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at