chr6-32519641-C-T

Variant names:

• chr6-32519641-C-T
• rs771206465
• NM_002125.4:c.381G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002125.4(HLA-DRB5):​c.381G>A​(p.Lys127Lys) 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00096 (2 hom., cov: 3)
  • Exomes 𝑓: 0.00051 (14 hom.)
• Consequence: HLA-DRB5 NM_002125.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63
• Publications: 1 publications found

Genes affected

HLA-DRB5 (HGNC:4953): (major histocompatibility complex, class II, DR beta 5) HLA-DRB5 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. There are multiple pseudogenes of this gene. [provided by RefSeq, Feb 2020]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 6-32519641-C-T is Benign according to our data. Variant chr6-32519641-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656452.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.63 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002125.4. 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
	HLA-DRB5	NM_002125.4	MANE Select	c.381G>A	p.Lys127Lys	synonymous	Exon 3 of 6	NP_002116.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRB5	ENST00000374975.4	TSL:6 MANE Select	c.381G>A	p.Lys127Lys	synonymous	Exon 3 of 6	ENSP00000364114.3	Q30154
	HLA-DRB5	ENST00000943826.1		c.381G>A	p.Lys127Lys	synonymous	Exon 3 of 5	ENSP00000613885.1
	HLA-DRB5	ENST00000943827.1		c.354G>A	p.Lys118Lys	synonymous	Exon 3 of 6	ENSP00000613886.1

Frequencies

GnomAD3 genomes AF: 0.000936 AC: 39 AN: 41672 Hom.: 2 Cov.: 3

Gnomad AFR AF: 0.000452

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00446

Gnomad ASJ AF: 0.00319

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000381

Gnomad MID AF: 0.0161

Gnomad NFE AF: 0.000752

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 12 AN: 88952 AF XY: 0.0000818

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000360

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000252

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000511 AC: 310 AN: 606672 Hom.: 14 Cov.: 7 AF XY: 0.000511 AC XY: 158 AN XY: 309496

African (AFR) AF: 0.000636 AC: 8 AN: 12578

American (AMR) AF: 0.00218 AC: 43 AN: 19718

Ashkenazi Jewish (ASJ) AF: 0.000622 AC: 7 AN: 11250

East Asian (EAS) AF: 0.00 AC: 0 AN: 24270

South Asian (SAS) AF: 0.000349 AC: 15 AN: 43022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29632

Middle Eastern (MID) AF: 0.0146 AC: 33 AN: 2268

European-Non Finnish (NFE) AF: 0.000390 AC: 170 AN: 435788

Other (OTH) AF: 0.00121 AC: 34 AN: 28146

GnomAD4 genome AF: 0.000959 AC: 40 AN: 41698 Hom.: 2 Cov.: 3 AF XY: 0.00112 AC XY: 23 AN XY: 20518

African (AFR) AF: 0.000542 AC: 6 AN: 11072

American (AMR) AF: 0.00445 AC: 15 AN: 3368

Ashkenazi Jewish (ASJ) AF: 0.00319 AC: 2 AN: 626

East Asian (EAS) AF: 0.00 AC: 0 AN: 1542

South Asian (SAS) AF: 0.00 AC: 0 AN: 1808

European-Finnish (FIN) AF: 0.000381 AC: 1 AN: 2622

Middle Eastern (MID) AF: 0.0167 AC: 1 AN: 60

European-Non Finnish (NFE) AF: 0.000752 AC: 15 AN: 19946

Other (OTH) AF: 0.00 AC: 0 AN: 484

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.6
DANN	Benign	0.52
PhyloP100		-1.6
Mutation Taster		=99/1	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: rs771206465; hg19: chr6-32487418;