rs8005468

Variant names:

• chr14-106686431-G-A
• rs8005468
• unassigned_transcript_2623:c.112C>T
• IGHVII-67-1 p.Arg38Cys

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 4 publications found

Genes affected

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

IGH (HGNC:5477):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522410.1. 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
	IGHVII-67-1	ENST00000522410.1	TSL:6	n.*86C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36952 AN: 151794 Hom.: 4981 Cov.: 33

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: 2 AN: 10 Hom.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 2 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.243 AC: 36973 AN: 151910 Hom.: 4984 Cov.: 33 AF XY: 0.248 AC XY: 18438 AN XY: 74246

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: 89 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17644 AN: 67930

Other (OTH) AF: 0.255 AC: 536 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.5
DANN	Benign	0.44
PhyloP100		-1.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs8005468;

hg19: chr14-107142448;