chr20-35279894-A-G

Variant names:

• chr20-35279894-A-G
• rs619865
• NM_002212.4:c.546+48T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 46 publications found

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]

EIF6 Gene-Disease associations (from GenCC):

• Shwachman-Diamond syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox

ENSG00000261582 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002212.4. 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
	EIF6	NM_002212.4	MANE Select	c.546+48T>C		intron	N/A	NP_002203.1
	EIF6	NM_001267810.1		c.546+48T>C		intron	N/A	NP_001254739.1
	EIF6	NM_181468.2		c.546+48T>C		intron	N/A	NP_852133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF6	ENST00000374450.8	TSL:1 MANE Select	c.546+48T>C		intron	N/A	ENSP00000363574.3
	EIF6	ENST00000374436.7	TSL:1	c.546+48T>C		intron	N/A	ENSP00000363559.3
	ENSG00000261582	ENST00000444717.1	TSL:3	n.102+48T>C		intron	N/A	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

GnomAD2 exomes AF: 0.940 AC: 228163 AN: 242828 AF XY: 0.938

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 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

African (AFR) AF: 0.985 AC: 32662 AN: 33164

American (AMR) AF: 0.970 AC: 42608 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 23570 AN: 25044

East Asian (EAS) AF: 1.00 AC: 39464 AN: 39472

South Asian (SAS) AF: 0.948 AC: 80138 AN: 84504

European-Finnish (FIN) AF: 0.954 AC: 50488 AN: 52896

Middle Eastern (MID) AF: 0.948 AC: 5372 AN: 5666

European-Non Finnish (NFE) AF: 0.887 AC: 977102 AN: 1101328

Other (OTH) AF: 0.912 AC: 54424 AN: 59660

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

African (AFR) AF: 0.983 AC: 40825 AN: 41536

American (AMR) AF: 0.951 AC: 14540 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3270 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5182

South Asian (SAS) AF: 0.957 AC: 4609 AN: 4816

European-Finnish (FIN) AF: 0.953 AC: 10116 AN: 10614

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61369 AN: 68018

Other (OTH) AF: 0.953 AC: 2013 AN: 2112

Alfa AF: 0.916 Hom.: 235694

Bravo AF: 0.941

Asia WGS AF: 0.984 AC: 3423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		-0.093
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

Other links and lift over

dbSNP: rs619865; hg19: chr20-33867697;