14-106680831-A-G

Variant names:

• chr14-106680831-A-G
• rs2011167
• unassigned_transcript_2622:c.129T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000000000(IGHV1-67):​c.129T>C​(p.Thr43Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 770,484 control chromosomes in the GnomAD database, including 7,335 homozygotes. 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: 𝑓 0.15 (1686 hom., cov: 32)
  • Exomes 𝑓: 0.13 (5649 hom.)
• Consequence: IGHV1-67 ENST00000000000 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 2 publications found

Genes affected

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

IGH (HGNC:5477):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-0.824 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22125 AN: 152040 Hom.: 1679 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.132 AC: 81496 AN: 618330 Hom.: 5649 Cov.: 0 AF XY: 0.132 AC XY: 44504 AN XY: 336996

African (AFR) AF: 0.175 AC: 3061 AN: 17478

American (AMR) AF: 0.140 AC: 6073 AN: 43228

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3108 AN: 20490

East Asian (EAS) AF: 0.133 AC: 4754 AN: 35700

South Asian (SAS) AF: 0.139 AC: 9626 AN: 69382

European-Finnish (FIN) AF: 0.125 AC: 6501 AN: 51802

Middle Eastern (MID) AF: 0.197 AC: 806 AN: 4086

European-Non Finnish (NFE) AF: 0.125 AC: 42991 AN: 343848

Other (OTH) AF: 0.142 AC: 4576 AN: 32316

GnomAD4 genome AF: 0.146 AC: 22153 AN: 152154 Hom.: 1686 Cov.: 32 AF XY: 0.146 AC XY: 10862 AN XY: 74372

African (AFR) AF: 0.174 AC: 7225 AN: 41496

American (AMR) AF: 0.160 AC: 2452 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 589 AN: 3470

East Asian (EAS) AF: 0.159 AC: 816 AN: 5148

South Asian (SAS) AF: 0.129 AC: 622 AN: 4814

European-Finnish (FIN) AF: 0.126 AC: 1332 AN: 10608

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8594 AN: 68004

Other (OTH) AF: 0.164 AC: 346 AN: 2112

Alfa AF: 0.136 Hom.: 180

Bravo AF: 0.150

Asia WGS AF: 0.139 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.2
DANN	Benign	0.45
PhyloP100		-0.82

Splicing

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

Other links and lift over

dbSNP: rs2011167; hg19: chr14-107136848; COSMIC: COSV69868635;