ENST00000486568.5:c.115+100T>C

Variant names:

• chr3-158732628-T-C
• rs6441224
• ENST00000486568.5:c.115+100T>C

Variant summary

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

The ENST00000486568.5(MFSD1):​c.115+100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,328,144 control chromosomes in the GnomAD database, including 193,198 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 0.58 (26264 hom., cov: 33)
  • Exomes 𝑓: 0.53 (166934 hom.)
• Consequence: MFSD1 ENST00000486568.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 11 publications found

Genes affected

MFSD1 (HGNC:25874): (major facilitator superfamily domain containing 1) Predicted to enable protein homodimerization activity. Predicted to be involved in protein localization to lysosome and protein stabilization. Predicted to be located in lysosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000240207 (HGNC:):

RARRES1 (HGNC:9867): (retinoic acid receptor responder 1) This gene was identified as a retinoid acid (RA) receptor-responsive gene. It encodes a type 1 membrane protein. The expression of this gene is upregulated by tazarotene as well as by retinoic acid receptors. The expression of this gene is found to be downregulated in prostate cancer, which is caused by the methylation of its promoter and CpG island. Alternatively spliced transcript variant encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000486568.5. 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
	LOC100287290	NR_171780.1		n.168+100T>C		intron	N/A
	LOC100287290	NR_171781.1		n.168+100T>C		intron	N/A
	LOC100287290	NR_171782.1		n.168+100T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD1	ENST00000486568.5	TSL:4	c.115+100T>C		intron	N/A	ENSP00000417414.1
	MFSD1	ENST00000491804.1	TSL:5	c.115+100T>C		intron	N/A	ENSP00000420699.1
	ENSG00000240207	ENST00000465477.6	TSL:5	n.202+100T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87884 AN: 151976 Hom.: 26216 Cov.: 33

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.531 AC: 624232 AN: 1176050 Hom.: 166934 Cov.: 34 AF XY: 0.533 AC XY: 302643 AN XY: 568268

African (AFR) AF: 0.740 AC: 16727 AN: 22612

American (AMR) AF: 0.492 AC: 5692 AN: 11566

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 8345 AN: 15342

East Asian (EAS) AF: 0.337 AC: 8489 AN: 25172

South Asian (SAS) AF: 0.603 AC: 32217 AN: 53422

European-Finnish (FIN) AF: 0.494 AC: 13230 AN: 26786

Middle Eastern (MID) AF: 0.603 AC: 1912 AN: 3172

European-Non Finnish (NFE) AF: 0.528 AC: 512122 AN: 970732

Other (OTH) AF: 0.540 AC: 25498 AN: 47246

GnomAD4 genome AF: 0.578 AC: 87985 AN: 152094 Hom.: 26264 Cov.: 33 AF XY: 0.577 AC XY: 42884 AN XY: 74344

African (AFR) AF: 0.730 AC: 30328 AN: 41528

American (AMR) AF: 0.503 AC: 7701 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1748 AN: 5132

South Asian (SAS) AF: 0.600 AC: 2896 AN: 4830

European-Finnish (FIN) AF: 0.503 AC: 5325 AN: 10580

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36272 AN: 67946

Other (OTH) AF: 0.563 AC: 1188 AN: 2112

Alfa AF: 0.565 Hom.: 3066

Bravo AF: 0.583

Asia WGS AF: 0.534 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.2
DANN	Benign	0.67
PhyloP100		-0.12
PromoterAI		0.19	Neutral
Mutation Taster		=300/0	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: rs6441224; hg19: chr3-158450417; COSMIC: COSV52963182; COSMIC: COSV52963182;