2-190482584-G-T

Variant names:

• chr2-190482584-G-T
• rs12613365
• NM_017694.4:c.1631-6073G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017694.4(MFSD6):​c.1631-6073G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,770 control chromosomes in the GnomAD database, including 7,492 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 0.30 (7492 hom., cov: 30)
• Consequence: MFSD6 NM_017694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 8 publications found

Genes affected

MFSD6 (HGNC:24711): (major facilitator superfamily domain containing 6) Predicted to enable MHC class I protein binding activity and MHC class I receptor activity. Predicted to be involved in antigen processing and presentation of exogenous peptide antigen via MHC class I. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

NEMP2 (HGNC:33700): (nuclear envelope integral membrane protein 2) Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD6	NM_017694.4	c.1631-6073G>T		intron_variant	Intron 4 of 7	ENST00000392328.6	NP_060164.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD6	ENST00000392328.6	c.1631-6073G>T		intron_variant	Intron 4 of 7	2	NM_017694.4	ENSP00000376141.1
MFSD6	ENST00000281416.11	c.1631-6073G>T		intron_variant	Intron 2 of 5	1		ENSP00000281416.7
MFSD6	ENST00000434582.5	c.236-6073G>T		intron_variant	Intron 2 of 6	5		ENSP00000397276.1
MFSD6	ENST00000444317.1	c.17-6073G>T		intron_variant	Intron 2 of 4	4		ENSP00000406837.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45234 AN: 151652 Hom.: 7479 Cov.: 30

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45275 AN: 151770 Hom.: 7492 Cov.: 30 AF XY: 0.311 AC XY: 23030 AN XY: 74160

African (AFR) AF: 0.270 AC: 11162 AN: 41360

American (AMR) AF: 0.459 AC: 7013 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3468

East Asian (EAS) AF: 0.463 AC: 2381 AN: 5140

South Asian (SAS) AF: 0.221 AC: 1061 AN: 4808

European-Finnish (FIN) AF: 0.427 AC: 4470 AN: 10480

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17305 AN: 67930

Other (OTH) AF: 0.280 AC: 590 AN: 2108

Alfa AF: 0.309 Hom.: 1412

Bravo AF: 0.308

Asia WGS AF: 0.329 AC: 1150 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	3.4
DANN	Benign	0.70
PhyloP100		0.0010
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: rs12613365; hg19: chr2-191347310;