Genetic Variant TRGV5:p.Lys74Asn (chr7-38349487-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000390344.2(TRGV5):c.222G>T(p.Lys74Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 713,588 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 9 hom., cov: 22)

Exomes 𝑓: 0.00046 ( 51 hom. )

Consequence

TRGV5
ENST00000390344.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.424

Publications

1 publications found

Variant links:

Genes affected

TRGV5 (HGNC:12290): (T cell receptor gamma variable 5) Predicted to be involved in adaptive immune response and innate immune response. Predicted to be part of T cell receptor complex. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRGV5 links:

TRG (HGNC:12271):

TRG links:

TRG-AS1 (HGNC:48974): (T cell receptor gamma locus antisense RNA 1)

TRG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-38349487-C-A is Benign according to our data. Variant chr7-38349487-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657387.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390344.2. 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
	TRG-AS1	NR_040085.2		n.487-859C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRGV5	ENST00000390344.2	TSL:6	c.222G>T	p.Lys74Asn	missense	Exon 2 of 2	ENSP00000374867.2	A0A0B4J1U4
TRG-AS1	ENST00000629357.1	TSL:2	n.293-859C>A		intron	N/A
TRG-AS1	ENST00000668633.1		n.497-859C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000402

AC:

AN:

136896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000799

Gnomad AMI

AF:

0.00118

Gnomad AMR

AF:

0.00132

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:

0.000485

Gnomad OTH

AF:

0.00157

GnomAD2 exomes

AF:

0.000400

AC:

AN:

220058

AF XY:

0.000472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000716

Gnomad OTH exome

AF:

0.000540

GnomAD4 exome

AF:

0.000458

AC:

264

AN:

576582

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

170

AN XY:

315934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17118

American (AMR)

AF:

0.000504

AC:

AN:

39686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20190

East Asian (EAS)

AF:

0.00

AC:

AN:

34812

South Asian (SAS)

AF:

0.0000585

AC:

AN:

68414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34214

Middle Eastern (MID)

AF:

0.00274

AC:

AN:

4012

European-Non Finnish (NFE)

AF:

0.000630

AC:

206

AN:

327042

Other (OTH)

AF:

0.000740

AC:

AN:

31094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000401

AC:

AN:

137006

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

AN XY:

66382

show subpopulations

African (AFR)

AF:

0.0000797

AC:

AN:

37646

American (AMR)

AF:

0.00132

AC:

AN:

13640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3290

East Asian (EAS)

AF:

0.00

AC:

AN:

4840

South Asian (SAS)

AF:

0.00

AC:

AN:

4392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

61858

Other (OTH)

AF:

0.00155

AC:

AN:

1930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000480

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.5

(source)

DANN

Benign

0.89

PhyloP100

-0.42

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over