Genetic Variant IGHV1-67:p.Thr43Thr (chr14-106680831-A-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The ENST00000000000(IGHV1-67):c.129T>G(p.Thr43Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 618,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

IGHV1-67
ENST00000000000 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.824

Publications

0 publications found

Variant links:

Genes affected

IGHV1-67 (HGNC:5556): (immunoglobulin heavy variable 1-67 (pseudogene))

IGHV1-67 links:

IGH (HGNC:5477):

IGH links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP7

Synonymous conserved (PhyloP=-0.824 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHV1-67	unassigned_transcript_2622	c.129T>G	p.Thr43Thr	synonymous_variant	Exon 2 of 2
IGH		n.106680831A>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHV1-67	ENST00000519713.1 link	n.129T>G		non_coding_transcript_exon_variant	Exon 2 of 2	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000162

AC:

AN:

618602

Hom.:

Cov.:

AF XY:

0.00000297

AC XY:

AN XY:

337148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17488

American (AMR)

AF:

0.00

AC:

AN:

43250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20498

East Asian (EAS)

AF:

0.00

AC:

AN:

35714

South Asian (SAS)

AF:

0.00

AC:

AN:

69408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51818

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4088

European-Non Finnish (NFE)

AF:

0.00000291

AC:

AN:

343992

Other (OTH)

AF:

0.00

AC:

AN:

32346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.0

(source)

DANN

Benign

0.40

PhyloP100

-0.82

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over