rs17112078

Variant names:

• chr14-106823737-A-G
• rs17112078
• unassigned_transcript_2639:c.307T>C
• IGHV3-75 p.Leu103Leu

Variant summary

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

The ENST00000000000(IGHV3-75):​c.307T>C​(p.Leu103Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 160,244 control chromosomes in the GnomAD database, including 13,399 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 0.40 (12789 hom., cov: 32)
  • Exomes 𝑓: 0.36 (610 hom.)
• Consequence: IGHV3-75 ENST00000000000 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 6 publications found

Genes affected

IGHV3-75 (HGNC:5625): (immunoglobulin heavy variable 3-75 (pseudogene))

IGH (HGNC:5477):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.072 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523951.1. 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
	IGHV3-75	ENST00000523951.1	TSL:6	n.308T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60710 AN: 151818 Hom.: 12755 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.364 AC: 3023 AN: 8306 Hom.: 610 Cov.: 0 AF XY: 0.369 AC XY: 1668 AN XY: 4524

African (AFR) AF: 0.560 AC: 84 AN: 150

American (AMR) AF: 0.269 AC: 49 AN: 182

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 21 AN: 58

East Asian (EAS) AF: 0.309 AC: 60 AN: 194

South Asian (SAS) AF: 0.420 AC: 147 AN: 350

European-Finnish (FIN) AF: 0.359 AC: 1715 AN: 4778

Middle Eastern (MID) AF: 0.392 AC: 29 AN: 74

European-Non Finnish (NFE) AF: 0.366 AC: 818 AN: 2232

Other (OTH) AF: 0.347 AC: 100 AN: 288

GnomAD4 genome AF: 0.400 AC: 60803 AN: 151938 Hom.: 12789 Cov.: 32 AF XY: 0.401 AC XY: 29765 AN XY: 74264

African (AFR) AF: 0.535 AC: 22170 AN: 41408

American (AMR) AF: 0.328 AC: 5005 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1411 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1529 AN: 5166

South Asian (SAS) AF: 0.408 AC: 1962 AN: 4810

European-Finnish (FIN) AF: 0.370 AC: 3907 AN: 10558

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23707 AN: 67932

Other (OTH) AF: 0.334 AC: 707 AN: 2114

Alfa AF: 0.366 Hom.: 44582

Bravo AF: 0.400

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.18
PhyloP100		0.072

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: rs17112078;

hg19: chr14-107231967;