rs7646881

Variant names:

• chr3-158735490-C-A
• rs7646881
• ENST00000486568.5:c.115+2962C>A

Variant summary

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

The ENST00000486568.5(MFSD1):​c.115+2962C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,198 control chromosomes in the GnomAD database, including 3,321 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 0.20 (3321 hom., cov: 33)
• Consequence: MFSD1 ENST00000486568.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 19 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100287290	NR_171780.1		n.255+1453C>A		intron	N/A
	LOC100287290	NR_171781.1		n.255+1453C>A		intron	N/A
	LOC100287290	NR_171782.1		n.255+1453C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD1	ENST00000486568.5	TSL:4	c.115+2962C>A		intron	N/A	ENSP00000417414.1	C9JBA3
	MFSD1	ENST00000491804.1	TSL:5	c.202+1453C>A		intron	N/A	ENSP00000420699.1	C9JCH3
	ENSG00000240207	ENST00000465477.6	TSL:5	n.289+1453C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30525 AN: 152080 Hom.: 3316 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.201 AC: 30561 AN: 152198 Hom.: 3321 Cov.: 33 AF XY: 0.196 AC XY: 14557 AN XY: 74426

African (AFR) AF: 0.283 AC: 11764 AN: 41496

American (AMR) AF: 0.162 AC: 2479 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3468

East Asian (EAS) AF: 0.0145 AC: 75 AN: 5182

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4830

European-Finnish (FIN) AF: 0.0980 AC: 1039 AN: 10598

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12703 AN: 68006

Other (OTH) AF: 0.208 AC: 440 AN: 2114

Alfa AF: 0.192 Hom.: 12236

Bravo AF: 0.205

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.77
DANN	Benign	0.62
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7646881;

hg19: chr3-158453279;