rs7478728

chr11-320994-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000602429.1(ENSG00000251661):n.94+2248G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 145,372 control chromosomes in the GnomAD database, including 14,022 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 0.50 (14022 hom., cov: 32)
  • Exomes 𝑓: 0.55 (73185 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENST00000602429.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

Genes affected

(HGNC:):

IFITM3 (HGNC:5414): (interferon induced transmembrane protein 3) Interferon-induced transmembrane (IFITM) proteins are a family of interferon induced antiviral proteins. The family contains five members, including IFITM1, IFITM2 and IFITM3 and belong to the CD225 superfamily. The protein encoded by this gene restricts cellular entry by diverse viral pathogens, such as influenza A virus, Ebola virus and Sars-CoV-2. [provided by RefSeq, Nov 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105376505	XR_007062535.1	n.287+2248G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000602429.1	n.94+2248G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 72899 AN: 145252 Hom.: 14015 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.450

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.483

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.551 AC: 300420 AN: 545404 Hom.: 73185 Cov.: 7 AF XY: 0.547 AC XY: 156168 AN XY: 285270

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.592

Gnomad4 SAS exome AF: 0.486

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.542

GnomAD4 genome AF: 0.502 AC: 72957 AN: 145372 Hom.: 14022 Cov.: 32 AF XY: 0.504 AC XY: 35701 AN XY: 70892

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.483

Alfa AF: 0.553 Hom.: 2148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.5
Dann	Benign	0.78

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: rs7478728; hg19: chr11-320994; COSMIC: COSV67707427; COSMIC: COSV67707427;