chr14-106680831-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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000519713.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHV1-67	ENST00000519713.1	TSL:6	n.129T>C		non_coding_transcript_exon	Exon 2 of 2

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 v4.9

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;