rs6598045

Variant names:

• chr11-321001-A-G
• rs6598045
• ENST00000602429.2:n.115+2255A>G

Variant summary

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

The ENST00000679433.1(IFITM3):​c.-22-229T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 647,542 control chromosomes in the GnomAD database, including 5,161 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 0.21 (1040 hom., cov: 32)
  • Exomes 𝑓: 0.18 (4121 hom.)
• Consequence: IFITM3 ENST00000679433.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885
• Publications: 34 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFITM3	NM_021034.3	MANE Select	c.-188T>C		upstream_gene	N/A	NP_066362.2	Q01628
	IFITM3	NR_049759.2		n.-141T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFITM3-AS1	ENST00000602429.2	TSL:1	n.115+2255A>G		intron	N/A
	IFITM3	ENST00000526811.4	TSL:5	c.-23+223T>C		intron	N/A	ENSP00000432108.1	E9PS44
	IFITM3	ENST00000602735.2	TSL:5	c.-22-229T>C		intron	N/A	ENSP00000473544.1	E9PS44

Frequencies

GnomAD3 genomes AF: 0.205 AC: 29273 AN: 142876 Hom.: 1042 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.176 AC: 88842 AN: 504548 Hom.: 4121 Cov.: 6 AF XY: 0.182 AC XY: 48045 AN XY: 264384

African (AFR) AF: 0.317 AC: 4483 AN: 14160

American (AMR) AF: 0.302 AC: 5979 AN: 19778

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 2205 AN: 13346

East Asian (EAS) AF: 0.158 AC: 5171 AN: 32672

South Asian (SAS) AF: 0.305 AC: 14493 AN: 47574

European-Finnish (FIN) AF: 0.0840 AC: 2356 AN: 28038

Middle Eastern (MID) AF: 0.224 AC: 450 AN: 2012

European-Non Finnish (NFE) AF: 0.153 AC: 48807 AN: 319688

Other (OTH) AF: 0.180 AC: 4898 AN: 27280

GnomAD4 genome AF: 0.205 AC: 29330 AN: 142994 Hom.: 1040 Cov.: 32 AF XY: 0.205 AC XY: 14350 AN XY: 70018

African (AFR) AF: 0.309 AC: 12065 AN: 39058

American (AMR) AF: 0.259 AC: 3776 AN: 14554

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 556 AN: 3272

East Asian (EAS) AF: 0.172 AC: 884 AN: 5134

South Asian (SAS) AF: 0.286 AC: 1318 AN: 4602

European-Finnish (FIN) AF: 0.0824 AC: 824 AN: 10000

Middle Eastern (MID) AF: 0.234 AC: 67 AN: 286

European-Non Finnish (NFE) AF: 0.148 AC: 9361 AN: 63286

Other (OTH) AF: 0.214 AC: 428 AN: 2004

Alfa AF: 0.186 Hom.: 115

Asia WGS AF: 0.234 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.55
PhyloP100		-0.89
PromoterAI		0.20	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6598045;

hg19: chr11-321001;

COSMIC: COSV67707433;

COSMIC: COSV67707433;