7-6035813-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000199389.11(EIF2AK1):​c.1332+1611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,550,174 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 21 hom. )

Consequence

EIF2AK1
ENST00000199389.11 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.807
Variant links:
Genes affected
ANKRD61 (HGNC:22467): (ankyrin repeat domain 61) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
EIF2AK1 (HGNC:24921): (eukaryotic translation initiation factor 2 alpha kinase 1) The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 7-6035813-C-T is Benign according to our data. Variant chr7-6035813-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657295.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 327 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANKRD61NM_001271700.2 linkuse as main transcriptc.684C>T p.Asn228Asn synonymous_variant 3/3 ENST00000409061.2 NP_001258629.1 A6NGH8
EIF2AK1NM_014413.4 linkuse as main transcriptc.1332+1611G>A intron_variant ENST00000199389.11 NP_055228.2 Q9BQI3-1A0A024QZU1
EIF2AK1NM_001134335.2 linkuse as main transcriptc.1329+1611G>A intron_variant NP_001127807.1 Q9BQI3-2
EIF2AK1XM_047420200.1 linkuse as main transcriptc.708+1611G>A intron_variant XP_047276156.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANKRD61ENST00000409061.2 linkuse as main transcriptc.684C>T p.Asn228Asn synonymous_variant 3/35 NM_001271700.2 ENSP00000386502.1 A6NGH8
EIF2AK1ENST00000199389.11 linkuse as main transcriptc.1332+1611G>A intron_variant 1 NM_014413.4 ENSP00000199389.6 Q9BQI3-1

Frequencies

GnomAD3 genomes
AF:
0.00215
AC:
327
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000917
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00744
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00319
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00209
AC:
313
AN:
149760
Hom.:
2
AF XY:
0.00196
AC XY:
157
AN XY:
80252
show subpopulations
Gnomad AFR exome
AF:
0.000283
Gnomad AMR exome
AF:
0.00118
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000186
Gnomad SAS exome
AF:
0.000758
Gnomad FIN exome
AF:
0.00454
Gnomad NFE exome
AF:
0.00319
Gnomad OTH exome
AF:
0.00228
GnomAD4 exome
AF:
0.00312
AC:
4355
AN:
1397860
Hom.:
21
Cov.:
30
AF XY:
0.00301
AC XY:
2073
AN XY:
689284
show subpopulations
Gnomad4 AFR exome
AF:
0.000697
Gnomad4 AMR exome
AF:
0.00121
Gnomad4 ASJ exome
AF:
0.0000397
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000808
Gnomad4 FIN exome
AF:
0.00637
Gnomad4 NFE exome
AF:
0.00349
Gnomad4 OTH exome
AF:
0.00263
GnomAD4 genome
AF:
0.00215
AC:
327
AN:
152314
Hom.:
0
Cov.:
32
AF XY:
0.00219
AC XY:
163
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.000916
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00744
Gnomad4 NFE
AF:
0.00319
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00262
Hom.:
1
Bravo
AF:
0.00173

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022ANKRD61: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
11
DANN
Benign
0.82

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138987807; hg19: chr7-6075444; COSMIC: COSV99552518; API