rs6441224

Positions:

• chr3-158732628-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100287290	NR_171780.1	n.168+100T>C		intron_variant
LOC100287290	NR_171781.1	n.168+100T>C		intron_variant
LOC100287290	NR_171782.1	n.168+100T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD1	ENST00000486568.5	c.115+100T>C		intron_variant		4		ENSP00000417414.1
MFSD1	ENST00000491804.1	c.115+100T>C		intron_variant		5		ENSP00000420699.1
ENSG00000240207	ENST00000465477.5	n.202+100T>C		intron_variant		5

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

Gnomad4 AFR exome AF: 0.740

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.540

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

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.563

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.2
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs6441224; hg19: chr3-158450417; COSMIC: COSV52963182; COSMIC: COSV52963182;