dbSNP rs3738668: MFSD2A:c.-246C>A (chr1-39955047-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032793.5(MFSD2A):c.-246C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 370,050 control chromosomes in the GnomAD database, including 3,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 1134 hom., cov: 31)

Exomes 𝑓: 0.068 ( 2863 hom. )

Consequence

MFSD2A
NM_032793.5 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.132

Publications

3 publications found

Variant links:

Genes affected

MFSD2A (HGNC:25897): (MFSD2 lysolipid transporter A, lysophospholipid) The protein encoded by this gene is a transmembrane protein and sodium-dependent lysophosphatidylcholine transporter. The encoded protein is involved in the establishment of the blood-brain barrier and is required for brain growth and function. Defects in this gene are a cause of a progressive microcephaly syndrome. [provided by RefSeq, Mar 2017]

MFSD2A Gene-Disease associations (from GenCC):

microcephaly 15, primary, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MFSD2A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_032793.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-39955047-C-A is Benign according to our data. Variant chr1-39955047-C-A is described in ClinVar as Benign. ClinVar VariationId is 1223952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032793.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MFSD2A	NM_032793.5	MANE Select	c.-246C>A	upstream_gene	N/A	NP_116182.2
MFSD2A	NM_001136493.3		c.-246C>A	upstream_gene	N/A	NP_001129965.1	Q8NA29-1
MFSD2A	NM_001349821.2		c.-246C>A	upstream_gene	N/A	NP_001336750.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MFSD2A	ENST00000372811.10	TSL:1 MANE Select	c.-246C>A	upstream_gene	N/A	ENSP00000361898.6	Q8NA29-2
MFSD2A	ENST00000483824.5	TSL:1	n.-111C>A	upstream_gene	N/A
MFSD2A	ENST00000372809.5	TSL:2	c.-246C>A	upstream_gene	N/A	ENSP00000361895.5	Q8NA29-1

Frequencies

GnomAD3 genomes

AF:

0.0790

AC:

11942

AN:

151172

Hom.:

1128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.0746

Gnomad FIN

AF:

0.0390

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00488

Gnomad OTH

AF:

0.0749

GnomAD4 exome

AF:

0.0681

AC:

14891

AN:

218760

Hom.:

2863

AF XY:

0.0649

AC XY:

7193

AN XY:

110810

show subpopulations

African (AFR)

AF:

0.162

AC:

1049

AN:

6484

American (AMR)

AF:

0.132

AC:

839

AN:

6362

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

AN:

8428

East Asian (EAS)

AF:

0.499

AC:

10297

AN:

20654

South Asian (SAS)

AF:

0.0697

AC:

150

AN:

2152

European-Finnish (FIN)

AF:

0.0389

AC:

712

AN:

18298

Middle Eastern (MID)

AF:

0.0189

AC:

AN:

1164

European-Non Finnish (NFE)

AF:

0.00520

AC:

731

AN:

140554

Other (OTH)

AF:

0.0679

AC:

995

AN:

14664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

426

852

1279

1705

2131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.0791

AC:

11968

AN:

151290

Hom.:

1134

Cov.:

AF XY:

0.0833

AC XY:

6154

AN XY:

73880

show subpopulations

African (AFR)

AF:

0.160

AC:

6601

AN:

41182

American (AMR)

AF:

0.122

AC:

1850

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3462

East Asian (EAS)

AF:

0.443

AC:

2221

AN:

5018

South Asian (SAS)

AF:

0.0740

AC:

352

AN:

4754

European-Finnish (FIN)

AF:

0.0390

AC:

411

AN:

10528

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00488

AC:

331

AN:

67840

Other (OTH)

AF:

0.0750

AC:

157

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

464

928

1393

1857

2321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0443

Hom.:

Bravo

AF:

0.0914

Asia WGS

AF:

0.272

AC:

944

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

-0.13

PromoterAI

-0.099

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over