Genetic Variant IGHVII-67-1:p.Arg38Cys (chr14-106686431-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000000000(IGHVII-67-1):c.112C>T(p.Arg38Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,920 control chromosomes in the GnomAD database, including 4,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4984 hom., cov: 33)

Exomes 𝑓: 0.20 ( 0 hom. )

Consequence

IGHVII-67-1
ENST00000000000 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.62

Publications

4 publications found

Variant links:

Genes affected

IGHVII-67-1 (HGNC:5689): (immunoglobulin heavy variable (II)-67-1 (pseudogene))

IGHVII-67-1 links:

IGH (HGNC:5477):

IGH links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHVII-67-1	unassigned_transcript_2623	c.112C>T	p.Arg38Cys	missense_variant	Exon 1 of 1
IGH		n.106686431G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHVII-67-1	ENST00000522410.1 link	n.*86C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36952

AN:

151794

Hom.:

4981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.308

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.257

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.243

AC:

36973

AN:

151910

Hom.:

4984

Cov.:

AF XY:

0.248

AC XY:

18438

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.160

AC:

6650

AN:

41436

American (AMR)

AF:

0.244

AC:

3719

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

1114

AN:

3470

East Asian (EAS)

AF:

0.347

AC:

1787

AN:

5154

South Asian (SAS)

AF:

0.491

AC:

2363

AN:

4814

European-Finnish (FIN)

AF:

0.272

AC:

2869

AN:

10538

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.260

AC:

17644

AN:

67930

Other (OTH)

AF:

0.255

AC:

536

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1388

2777

4165

5554

6942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.245

Hom.:

1150

Bravo

AF:

0.235

Asia WGS

AF:

0.384

AC:

1337

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.5

(source)

DANN

Benign

0.44

PhyloP100

-1.6

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over