14-106537943-C-T

Variant names:

• chr14-106537943-C-T
• rs7148607
• ENST00000390624.3:c.220G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000390624.3(IGHV3-48):​c.220G>A​(p.Gly74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.49 (7494 hom., cov: 31)
  • Exomes 𝑓: 0.51 (33475 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGHV3-48 ENST00000390624.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 5 publications found

Genes affected

IGHV3-48 (HGNC:5606): (immunoglobulin heavy variable 3-48) Predicted to enable antigen binding activity and immunoglobulin receptor binding activity. Predicted to be involved in several processes, including activation of immune response; defense response to other organism; and phagocytosis. Predicted to be located in extracellular region and plasma membrane. Predicted to be part of immunoglobulin complex, circulating. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

IGH (HGNC:5477):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHV3-48	unassigned_transcript_2596	c.220G>A	p.Gly74Ser	missense_variant	Exon 2 of 2
IGH		n.106537943C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHV3-48	ENST00000390624.3	c.220G>A	p.Gly74Ser	missense_variant	Exon 2 of 2	6		ENSP00000375033.2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 68338 AN: 139104 Hom.: 7487 Cov.: 31

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.512

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.509 AC: 315216 AN: 618744 Hom.: 33475 Cov.: 0 AF XY: 0.512 AC XY: 172450 AN XY: 336732

African (AFR) AF: 0.436 AC: 7517 AN: 17252

American (AMR) AF: 0.519 AC: 22271 AN: 42914

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 11404 AN: 20654

East Asian (EAS) AF: 0.442 AC: 15695 AN: 35476

South Asian (SAS) AF: 0.545 AC: 37688 AN: 69190

European-Finnish (FIN) AF: 0.453 AC: 23763 AN: 52456

Middle Eastern (MID) AF: 0.571 AC: 2324 AN: 4068

European-Non Finnish (NFE) AF: 0.517 AC: 177868 AN: 344152

Other (OTH) AF: 0.512 AC: 16686 AN: 32582

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.491 AC: 68381 AN: 139224 Hom.: 7494 Cov.: 31 AF XY: 0.489 AC XY: 33238 AN XY: 67964

African (AFR) AF: 0.432 AC: 16388 AN: 37974

American (AMR) AF: 0.522 AC: 7220 AN: 13828

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1808 AN: 3224

East Asian (EAS) AF: 0.438 AC: 2035 AN: 4648

South Asian (SAS) AF: 0.569 AC: 2487 AN: 4374

European-Finnish (FIN) AF: 0.447 AC: 4318 AN: 9658

Middle Eastern (MID) AF: 0.648 AC: 162 AN: 250

European-Non Finnish (NFE) AF: 0.521 AC: 32535 AN: 62506

Other (OTH) AF: 0.510 AC: 978 AN: 1918

Alfa AF: 0.846 Hom.: 3933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.6
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs7148607; hg19: chr14-106993945;