rs3103778

Variant names:

• chr1-39968099-A-G
• rs3103778
• NM_032793.5:c.1208+183A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-39968099-A-G
• chr1-39968099-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0740
• Publications: 22 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1226321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD2A	NM_032793.5	MANE Select	c.1208+183A>G		intron	N/A	NP_116182.2
	MFSD2A	NM_001136493.3		c.1247+183A>G		intron	N/A	NP_001129965.1	Q8NA29-1
	MFSD2A	NM_001349821.2		c.1202+183A>G		intron	N/A	NP_001336750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD2A	ENST00000372811.10	TSL:1 MANE Select	c.1208+183A>G		intron	N/A	ENSP00000361898.6	Q8NA29-2
	MFSD2A	ENST00000483824.5	TSL:1	n.1147-235A>G		intron	N/A
	MFSD2A	ENST00000372809.5	TSL:2	c.1247+183A>G		intron	N/A	ENSP00000361895.5	Q8NA29-1

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

African (AFR) AF: 0.317 AC: 4151 AN: 13100

American (AMR) AF: 0.511 AC: 9635 AN: 18844

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 7251 AN: 14010

East Asian (EAS) AF: 0.524 AC: 16492 AN: 31478

South Asian (SAS) AF: 0.700 AC: 31796 AN: 45402

European-Finnish (FIN) AF: 0.481 AC: 14873 AN: 30946

Middle Eastern (MID) AF: 0.509 AC: 1046 AN: 2054

European-Non Finnish (NFE) AF: 0.524 AC: 160208 AN: 306022

Other (OTH) AF: 0.520 AC: 14279 AN: 27448

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

African (AFR) AF: 0.315 AC: 13015 AN: 41340

American (AMR) AF: 0.499 AC: 7620 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1808 AN: 3466

East Asian (EAS) AF: 0.559 AC: 2870 AN: 5138

South Asian (SAS) AF: 0.706 AC: 3398 AN: 4812

European-Finnish (FIN) AF: 0.476 AC: 5027 AN: 10564

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35351 AN: 67890

Other (OTH) AF: 0.450 AC: 948 AN: 2108

Alfa AF: 0.501 Hom.: 80423

Bravo AF: 0.453

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.56
DANN	Benign	0.50
PhyloP100		-0.074
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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