dbSNP rs6441224: MFSD1:c.115+100T>C (chr3-158732628-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.119

Publications

11 publications found

Variant links:

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]

MFSD1 links:

ENSG00000240207 (HGNC:):

ENSG00000240207 links:

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]

RARRES1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARRES1	NM_206963.2 link	c.-213A>G		upstream_gene_variant		ENST00000237696.10	NP_996846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARRES1	ENST00000237696.10 link	c.-213A>G		upstream_gene_variant		1	NM_206963.2	ENSP00000237696.5

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87884

AN:

151976

Hom.:

26216

Cov.:

show subpopulations

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.:

AF XY:

0.533

AC XY:

302643

AN XY:

568268

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16790

33580

50369

67159

83949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16168

32336

48504

64672

80840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.578

AC:

87985

AN:

152094

Hom.:

26264

Cov.:

AF XY:

0.577

AC XY:

42884

AN XY:

74344

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1941

3882

5823

7764

9705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.67

PhyloP100

-0.12

PromoterAI

0.19

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over