chr14-106680856-G-T

Variant names:

• chr14-106680856-G-T
• rs1961901
• unassigned_transcript_2622:c.104C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000000000(IGHV1-67):​c.104C>A​(p.Ala35Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 768,722 control chromosomes in the GnomAD database, including 9,090 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 0.18 (2752 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6338 hom.)
• Consequence: IGHV1-67 ENST00000000000 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHV1-67	unassigned_transcript_2622	c.104C>A	p.Ala35Glu	missense_variant	Exon 2 of 2
IGH		n.106680856G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHV1-67	ENST00000519713.1	n.104C>A		non_coding_transcript_exon_variant	Exon 2 of 2	6

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26920 AN: 151960 Hom.: 2737 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.137 AC: 84718 AN: 616648 Hom.: 6338 Cov.: 0 AF XY: 0.137 AC XY: 45911 AN XY: 335928

African (AFR) AF: 0.283 AC: 4936 AN: 17460

American (AMR) AF: 0.148 AC: 6376 AN: 43222

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 3738 AN: 20294

East Asian (EAS) AF: 0.133 AC: 4760 AN: 35728

South Asian (SAS) AF: 0.139 AC: 9522 AN: 68734

European-Finnish (FIN) AF: 0.125 AC: 6471 AN: 51700

Middle Eastern (MID) AF: 0.214 AC: 872 AN: 4070

European-Non Finnish (NFE) AF: 0.126 AC: 43069 AN: 343120

Other (OTH) AF: 0.154 AC: 4974 AN: 32320

GnomAD4 genome AF: 0.177 AC: 26969 AN: 152074 Hom.: 2752 Cov.: 32 AF XY: 0.177 AC XY: 13128 AN XY: 74326

African (AFR) AF: 0.281 AC: 11660 AN: 41446

American (AMR) AF: 0.171 AC: 2607 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3472

East Asian (EAS) AF: 0.159 AC: 822 AN: 5160

South Asian (SAS) AF: 0.130 AC: 624 AN: 4816

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10602

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

European-Non Finnish (NFE) AF: 0.127 AC: 8637 AN: 67980

Other (OTH) AF: 0.187 AC: 393 AN: 2106

Alfa AF: 0.156 Hom.: 266

Bravo AF: 0.186

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs1961901; hg19: chr14-107136873; COSMIC: COSV69868636;