20-35279894-A-G

Position:

• chr20-35279894-A-G

Variant summary

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

The NM_002212.4(EIF6):​c.546+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,597,916 control chromosomes in the GnomAD database, including 658,225 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 0.94 (67317 hom., cov: 31)
  • Exomes 𝑓: 0.90 (590908 hom.)
• Consequence: EIF6 NM_002212.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

Genes affected

EIF6 (HGNC:6159): (eukaryotic translation initiation factor 6) Hemidesmosomes are structures which link the basal lamina to the intermediate filament cytoskeleton. An important functional component of hemidesmosomes is the integrin beta-4 subunit (ITGB4), a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and prevent the association of the 40S and 60S ribosomal subunits. Multiple non-protein coding transcript variants and variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

ENSG00000261582 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF6	NM_002212.4	c.546+48T>C		intron_variant		ENST00000374450.8	NP_002203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF6	ENST00000374450.8	c.546+48T>C		intron_variant		1	NM_002212.4	ENSP00000363574.3
ENSG00000261582	ENST00000444717.1	n.102+48T>C		intron_variant		3		ENSP00000489186.1

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142922 AN: 152132 Hom.: 67261 Cov.: 31

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.953

GnomAD3 exomes AF: 0.940 AC: 228163 AN: 242828 Hom.: 107391 AF XY: 0.938 AC XY: 122786 AN XY: 130938

Gnomad AFR exome AF: 0.986

Gnomad AMR exome AF: 0.971

Gnomad ASJ exome AF: 0.942

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.952

Gnomad FIN exome AF: 0.954

Gnomad NFE exome AF: 0.907

Gnomad OTH exome AF: 0.941

GnomAD4 exome AF: 0.903 AC: 1305828 AN: 1445666 Hom.: 590908 Cov.: 40 AF XY: 0.905 AC XY: 648901 AN XY: 716828

Gnomad4 AFR exome AF: 0.985

Gnomad4 AMR exome AF: 0.970

Gnomad4 ASJ exome AF: 0.941

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.948

Gnomad4 FIN exome AF: 0.954

Gnomad4 NFE exome AF: 0.887

Gnomad4 OTH exome AF: 0.912

GnomAD4 genome AF: 0.939 AC: 143036 AN: 152250 Hom.: 67317 Cov.: 31 AF XY: 0.942 AC XY: 70161 AN XY: 74448

Gnomad4 AFR AF: 0.983

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.942

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.953

Alfa AF: 0.913 Hom.: 107339

Bravo AF: 0.941

Asia WGS AF: 0.984 AC: 3423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.45

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: rs619865; hg19: chr20-33867697;