Genetic Variant NM_001025591.4:c.268G>C (chr19-34593578-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001025591.4(SCGB2B2):c.268G>C(p.Asp90His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,553,692 control chromosomes in the GnomAD database, including 3 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D90N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 3 hom. )

Consequence

SCGB2B2
NM_001025591.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Variant links:

Genes affected

SCGB2B2 (HGNC:27616): (secretoglobin family 2B member 2) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SCGB2B2 links:

SCGB1B2P (HGNC:20741): (secretoglobin family 1B member 2, pseudogene)

SCGB1B2P links:

ZNF807P (HGNC:33229): (zinc finger protein 807, pseudogene)

ZNF807P links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008254766).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCGB2B2	NM_001025591.4 link	c.268G>C	p.Asp90His	missense_variant	Exon 4 of 4	ENST00000601241.6	NP_001020762.1	Q4G0G5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCGB2B2	ENST00000601241.6 link	c.268G>C	p.Asp90His	missense_variant	Exon 4 of 4	2	NM_001025591.4	ENSP00000469876.1	Q4G0G5
SCGB2B2	ENST00000379204.2 link	c.268G>C	p.Asp90His	missense_variant	Exon 3 of 3	1		ENSP00000368502.2	Q4G0G5
SCGB2B2	ENST00000595326.1 link	n.394G>C		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000442

AC:

AN:

160552

Hom.:

AF XY:

0.000603

AC XY:

AN XY:

84564

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00309

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000186

AC:

261

AN:

1401568

Hom.:

Cov.:

AF XY:

0.000272

AC XY:

188

AN XY:

691520

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00305

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000370

Gnomad4 OTH exome

AF:

0.000241

GnomAD4 genome

AF:

0.000105

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.000324

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.0025

M_CAP

Benign

0.0013

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.3

D;.

REVEL

Benign

0.035

Polyphen

0.99

D;D

Vest4

0.086

MutPred

0.12

Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.014

MPC

0.31

ClinPred

0.19

GERP RS

0.046

Varity_R

0.38

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over