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6-31355138-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005514.8(HLA-B):c.981C>T(p.Val327=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 9)
Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

HLA-B
NM_005514.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.75
Variant links:
Genes affected
HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-31355138-G-A is Benign according to our data. Variant chr6-31355138-G-A is described in ClinVar as [Benign]. Clinvar id is 752503.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.75 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HLA-BNM_005514.8 linkuse as main transcriptc.981C>T p.Val327= synonymous_variant 5/8 ENST00000412585.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HLA-BENST00000412585.7 linkuse as main transcriptc.981C>T p.Val327= synonymous_variant 5/8 NM_005514.8 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000100
AC:
7
AN:
69898
Hom.:
0
Cov.:
9
show subpopulations
Gnomad AFR
AF:
0.000426
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000257
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000270
AC:
67
AN:
248126
Hom.:
0
AF XY:
0.000156
AC XY:
21
AN XY:
134298
show subpopulations
Gnomad AFR exome
AF:
0.00353
Gnomad AMR exome
AF:
0.000263
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000342
AC:
36
AN:
1052250
Hom.:
1
Cov.:
19
AF XY:
0.0000383
AC XY:
20
AN XY:
521550
show subpopulations
Gnomad4 AFR exome
AF:
0.000882
Gnomad4 AMR exome
AF:
0.0000996
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000474
Gnomad4 SAS exome
AF:
0.0000433
Gnomad4 FIN exome
AF:
0.0000286
Gnomad4 NFE exome
AF:
0.0000143
Gnomad4 OTH exome
AF:
0.0000238
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000100
AC:
7
AN:
69908
Hom.:
0
Cov.:
9
AF XY:
0.0000911
AC XY:
3
AN XY:
32916
show subpopulations
Gnomad4 AFR
AF:
0.000425
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000257
Gnomad4 OTH
AF:
0.00
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
5.3
Dann
Benign
0.51

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: rs2308518; hg19: chr6-31322915; COSMIC: COSV69521399; COSMIC: COSV69521399; API