rs7478728

Variant names:

• chr11-320994-G-A
• rs7478728
• ENST00000602429.2:n.115+2248G>A

Variant summary

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

The ENST00000602429.2(ENSG00000251661):​n.115+2248G>A variant causes a intron 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: ENSG00000251661 ENST00000602429.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 12 publications found

Genes affected

ENSG00000251661 (HGNC:58185):

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602429.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFITM3	NM_021034.3	MANE Select	c.-181C>T		upstream_gene	N/A	NP_066362.2
	IFITM3	NR_049759.2		n.-134C>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000251661	ENST00000602429.2	TSL:1	n.115+2248G>A		intron	N/A
	IFITM3	ENST00000526811.4	TSL:5	c.-22-222C>T		intron	N/A	ENSP00000432108.1
	IFITM3	ENST00000602735.2	TSL:5	c.-22-222C>T		intron	N/A	ENSP00000473544.1

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

African (AFR) AF: 0.408 AC: 6145 AN: 15072

American (AMR) AF: 0.576 AC: 11793 AN: 20482

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 6903 AN: 14076

East Asian (EAS) AF: 0.592 AC: 17877 AN: 30178

South Asian (SAS) AF: 0.486 AC: 23536 AN: 48382

European-Finnish (FIN) AF: 0.623 AC: 18894 AN: 30328

Middle Eastern (MID) AF: 0.477 AC: 1004 AN: 2106

European-Non Finnish (NFE) AF: 0.558 AC: 198532 AN: 355742

Other (OTH) AF: 0.542 AC: 15736 AN: 29038

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

African (AFR) AF: 0.396 AC: 15846 AN: 40050

American (AMR) AF: 0.501 AC: 7236 AN: 14434

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1588 AN: 3342

East Asian (EAS) AF: 0.536 AC: 2580 AN: 4814

South Asian (SAS) AF: 0.457 AC: 2071 AN: 4530

European-Finnish (FIN) AF: 0.604 AC: 5999 AN: 9940

Middle Eastern (MID) AF: 0.461 AC: 130 AN: 282

European-Non Finnish (NFE) AF: 0.553 AC: 36029 AN: 65104

Other (OTH) AF: 0.483 AC: 970 AN: 2010

Alfa AF: 0.553 Hom.: 2148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		-0.14
PromoterAI		-0.011	Neutral
Mutation Taster		=300/0	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: rs7478728; hg19: chr11-320994; COSMIC: COSV67707427; COSMIC: COSV67707427;