rs61764374

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBA1

The NM_004985.5(KRAS):​c.*4311A>G variant causes a 3 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 215,318 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 126 hom., cov: 32)
Exomes 𝑓: 0.042 ( 64 hom. )

Consequence

KRAS
NM_004985.5 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.35

Publications

6 publications found
Variant links:
Genes affected
KRAS (HGNC:6407): (KRAS proto-oncogene, GTPase) This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
ETFRF1 (HGNC:27052): (electron transfer flavoprotein regulatory factor 1) Involved in respiratory electron transport chain. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.18).
BP6
Variant 12-25205484-T-C is Benign according to our data. Variant chr12-25205484-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 308057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRASNM_004985.5 linkc.*4311A>G 3_prime_UTR_variant Exon 5 of 5 ENST00000311936.8 NP_004976.2 P01116-2A0A024RAV5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRASENST00000311936.8 linkc.*4311A>G 3_prime_UTR_variant Exon 5 of 5 1 NM_004985.5 ENSP00000308495.3 P01116-2

Frequencies

GnomAD3 genomes
AF:
0.0374
AC:
5643
AN:
151002
Hom.:
127
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00981
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.0299
Gnomad ASJ
AF:
0.0504
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0201
Gnomad FIN
AF:
0.0400
Gnomad MID
AF:
0.0669
Gnomad NFE
AF:
0.0585
Gnomad OTH
AF:
0.0447
GnomAD4 exome
AF:
0.0421
AC:
2705
AN:
64194
Hom.:
64
Cov.:
0
AF XY:
0.0437
AC XY:
1297
AN XY:
29664
show subpopulations
African (AFR)
AF:
0.00637
AC:
19
AN:
2982
American (AMR)
AF:
0.0252
AC:
48
AN:
1906
Ashkenazi Jewish (ASJ)
AF:
0.0551
AC:
225
AN:
4082
East Asian (EAS)
AF:
0.000108
AC:
1
AN:
9268
South Asian (SAS)
AF:
0.0258
AC:
14
AN:
542
European-Finnish (FIN)
AF:
0.0445
AC:
21
AN:
472
Middle Eastern (MID)
AF:
0.0682
AC:
27
AN:
396
European-Non Finnish (NFE)
AF:
0.0542
AC:
2123
AN:
39174
Other (OTH)
AF:
0.0423
AC:
227
AN:
5372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
127
254
382
509
636
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0373
AC:
5640
AN:
151124
Hom.:
126
Cov.:
32
AF XY:
0.0351
AC XY:
2597
AN XY:
73888
show subpopulations
African (AFR)
AF:
0.00978
AC:
396
AN:
40494
American (AMR)
AF:
0.0298
AC:
455
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.0504
AC:
175
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5194
South Asian (SAS)
AF:
0.0201
AC:
97
AN:
4828
European-Finnish (FIN)
AF:
0.0400
AC:
424
AN:
10590
Middle Eastern (MID)
AF:
0.0685
AC:
20
AN:
292
European-Non Finnish (NFE)
AF:
0.0585
AC:
3977
AN:
67982
Other (OTH)
AF:
0.0433
AC:
91
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
280
560
841
1121
1401
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
68
136
204
272
340
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0518
Hom.:
41
Bravo
AF:
0.0339
Asia WGS
AF:
0.0140
AC:
47
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Noonan syndrome Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.18
CADD
Benign
17
DANN
Benign
0.92
PhyloP100
7.3
Mutation Taster
=81/19
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs61764374; hg19: chr12-25358418; API