rs1219635237

Variant names:

• chr20-35284207-G-A
• rs1219635237
• NM_002212.4:c.162C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_181466.3(EIF6):​c.281C>T​(p.Pro94Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,447,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: EIF6 NM_181466.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.234
• Publications: 0 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]

FAM83C-AS1 (HGNC:16113): (FAM83C antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15437466).
• BP6: Variant 20-35284207-G-A is Benign according to our data. Variant chr20-35284207-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3507725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181466.3. 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
	EIF6	NM_002212.4	MANE Select	c.162C>T	p.Ala54Ala	synonymous	Exon 3 of 7	NP_002203.1	P56537-1
	EIF6	NM_181466.3		c.281C>T	p.Pro94Leu	missense	Exon 2 of 5	NP_852131.1	P56537-2
	EIF6	NM_001267810.1		c.162C>T	p.Ala54Ala	synonymous	Exon 3 of 7	NP_001254739.1	P56537-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF6	ENST00000374450.8	TSL:1 MANE Select	c.162C>T	p.Ala54Ala	synonymous	Exon 3 of 7	ENSP00000363574.3	P56537-1
	EIF6	ENST00000374436.7	TSL:1	c.162C>T	p.Ala54Ala	synonymous	Exon 2 of 6	ENSP00000363559.3	P56537-1
	EIF6	ENST00000447927.6	TSL:1	n.162C>T		non_coding_transcript_exon	Exon 3 of 6	ENSP00000411450.2	A0A0B4J1Y7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000484 AC: 7 AN: 1447740 Hom.: 0 Cov.: 31 AF XY: 0.00000418 AC XY: 3 AN XY: 717824

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39414

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86024

European-Finnish (FIN) AF: 0.0000202 AC: 1 AN: 49524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000453 AC: 5 AN: 1103560

Other (OTH) AF: 0.00 AC: 0 AN: 59842

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	14
DANN	Uncertain	1.0
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.23
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.077
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.029	D
Vest4		0.25
MutPred		0.64		Gain of sheet (P = 0.0028)
MVP		0.35
ClinPred		0.79	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=84/16	polymorphism

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: rs1219635237; hg19: chr20-33872010;