rs3103778

chr1-39968099-A-Gchr1-39968099-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032793.5(MFSD2A):c.1208+183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 641,086 control chromosomes in the GnomAD database, including 87,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17164 hom., cov: 30)
  • Exomes 𝑓: 0.53 (70293 hom.)
• Consequence: MFSD2A NM_032793.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0740

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-39968099-A-G is Benign according to our data. Variant chr1-39968099-A-G is described in ClinVar as [Benign]. Clinvar id is 1226321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFSD2A	NM_032793.5	c.1208+183A>G		intron_variant		ENST00000372811.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFSD2A	ENST00000372811.10	c.1208+183A>G		intron_variant		1	NM_032793.5	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70477 AN: 151662 Hom.: 17156 Cov.: 30

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.531 AC: 259731 AN: 489304 Hom.: 70293 Cov.: 5 AF XY: 0.540 AC XY: 138450 AN XY: 256588

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.511

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.520

GnomAD4 genome AF: 0.465 AC: 70518 AN: 151782 Hom.: 17164 Cov.: 30 AF XY: 0.467 AC XY: 34619 AN XY: 74174

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.450

Alfa AF: 0.508 Hom.: 35314

Bravo AF: 0.453

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.56
Dann	Benign	0.50

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: rs3103778; hg19: chr1-40433771; COSMIC: COSV65685245; COSMIC: COSV65685245;