11-321001-A-G

Position:

• chr11-321001-A-G

Variant summary

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

The ENST00000602429.1(ENSG00000251661):​n.94+2255A>G 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 0.182 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: ENST00000602429.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105376505	XR_007062535.1	n.287+2255A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000602429.1	n.94+2255A>G		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.0840

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.180

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

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.214

Alfa AF: 0.186 Hom.: 115

Asia WGS AF: 0.234 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.55

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: rs6598045; hg19: chr11-321001; COSMIC: COSV67707433; COSMIC: COSV67707433;