Genetic Variant IGHV3-48:p.Gly74Ser (chr14-106537943-C-T) – ACMG Classification: Likely_benign (-4 pts)

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

5 publications found

Variant links:

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]

IGHV3-48 links:

IGH (HGNC:5477):

IGH links:

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new If you want to explore the variant's impact on the transcript ENST00000390624.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390624.3. 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
	IGHV3-48	ENST00000390624.3	TSL:6	c.220G>A	p.Gly74Ser	missense	Exon 2 of 2	ENSP00000375033.2	P01763

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

68338

AN:

139104

Hom.:

7487

Cov.:

show subpopulations

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.:

AF XY:

0.512

AC XY:

172450

AN XY:

336732

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

6631

13261

19892

26522

33153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1304

2608

3912

5216

6520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.491

AC:

68381

AN:

139224

Hom.:

7494

Cov.:

AF XY:

0.489

AC XY:

33238

AN XY:

67964

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

1233

2465

3698

4930

6163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.846

Hom.:

3933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.6

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over