chr11-320988-G-A

Variant names:

• chr11-320988-G-A
• rs7479267
• ENST00000602429.2:n.115+2242G>A

Variant summary

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

The ENST00000679433.1(IFITM3):​c.-22-216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 145,174 control chromosomes in the GnomAD database, including 15,272 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 0.51 (15272 hom., cov: 32)
  • Exomes 𝑓: 0.56 (83596 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFITM3 ENST00000679433.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 11 publications found

Genes affected

IFITM3-AS1 (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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679433.1. 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.-175C>T		upstream_gene	N/A	NP_066362.2
	IFITM3	NR_049759.2		n.-128C>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFITM3-AS1	ENST00000602429.2	TSL:1	n.115+2242G>A		intron	N/A
	IFITM3	ENST00000526811.4	TSL:5	c.-22-216C>T		intron	N/A	ENSP00000432108.1
	IFITM3	ENST00000602735.2	TSL:5	c.-22-216C>T		intron	N/A	ENSP00000473544.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 73445 AN: 145074 Hom.: 15270 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.447

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.489

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.561 AC: 324880 AN: 578690 Hom.: 83596 Cov.: 8 AF XY: 0.559 AC XY: 168991 AN XY: 302434

African (AFR) AF: 0.396 AC: 6289 AN: 15894

American (AMR) AF: 0.604 AC: 13335 AN: 22072

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 7207 AN: 14418

East Asian (EAS) AF: 0.620 AC: 18956 AN: 30568

South Asian (SAS) AF: 0.505 AC: 25318 AN: 50114

European-Finnish (FIN) AF: 0.634 AC: 19897 AN: 31392

Middle Eastern (MID) AF: 0.490 AC: 1071 AN: 2186

European-Non Finnish (NFE) AF: 0.566 AC: 216239 AN: 381974

Other (OTH) AF: 0.551 AC: 16568 AN: 30072

GnomAD4 genome AF: 0.506 AC: 73485 AN: 145174 Hom.: 15272 Cov.: 32 AF XY: 0.508 AC XY: 35925 AN XY: 70724

African (AFR) AF: 0.383 AC: 15359 AN: 40052

American (AMR) AF: 0.514 AC: 7369 AN: 14328

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1627 AN: 3346

East Asian (EAS) AF: 0.569 AC: 2687 AN: 4724

South Asian (SAS) AF: 0.467 AC: 2105 AN: 4506

European-Finnish (FIN) AF: 0.614 AC: 6141 AN: 9994

Middle Eastern (MID) AF: 0.450 AC: 126 AN: 280

European-Non Finnish (NFE) AF: 0.562 AC: 36566 AN: 65058

Other (OTH) AF: 0.490 AC: 984 AN: 2010

Alfa AF: 0.407 Hom.: 700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.76
PhyloP100		0.083
PromoterAI		0.058	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: rs7479267; hg19: chr11-320988; COSMIC: COSV67706779; COSMIC: COSV67706779;