18-63915633-A-G

Variant names:

• chr18-63915633-A-G
• rs8097425
• NM_005024.3:c.123A>G

Variant summary

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

The NM_005024.3(SERPINB10):​c.123A>G​(p.Ile41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,611,480 control chromosomes in the GnomAD database, including 64,404 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.39 (15935 hom., cov: 32)
  • Exomes 𝑓: 0.24 (48469 hom.)
• Consequence: SERPINB10 NM_005024.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• Publications: 33 publications found

Genes affected

SERPINB10 (HGNC:8942): (serpin family B member 10) This gene is a member of the serpin peptidase inhibitor, clade B family and is found in a cluster of other similar genes on chromosome 18. The protein encoded by this gene appears to help control the regulation of protease functions during hematopoiesis. Variations in this gene may increase the risk of prostate cancer. [provided by RefSeq, Dec 2015]

ENSG00000289724 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.2298226E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB10	NM_005024.3	c.123A>G	p.Ile41Met	missense_variant	Exon 2 of 8	ENST00000238508.8	NP_005015.1
SERPINB10	XM_011526027.2	c.123A>G	p.Ile41Met	missense_variant	Exon 3 of 9		XP_011524329.1
SERPINB10	XM_017025793.2	c.123A>G	p.Ile41Met	missense_variant	Exon 2 of 8		XP_016881282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB10	ENST00000238508.8	c.123A>G	p.Ile41Met	missense_variant	Exon 2 of 8	1	NM_005024.3	ENSP00000238508.3
ENSG00000289724	ENST00000418725.1	c.678A>G	p.Ile226Met	missense_variant	Exon 6 of 7	5		ENSP00000392381.1
ENSG00000289724	ENST00000397996.6	c.759A>G	p.Ile253Met	missense_variant	Exon 7 of 8	5		ENSP00000381082.2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59032 AN: 151706 Hom.: 15875 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.374

GnomAD2 exomes AF: 0.301 AC: 75426 AN: 250218 AF XY: 0.284

Gnomad AFR exome AF: 0.767

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.236 AC: 345070 AN: 1459656 Hom.: 48469 Cov.: 33 AF XY: 0.235 AC XY: 170732 AN XY: 726168

African (AFR) AF: 0.775 AC: 25816 AN: 33316

American (AMR) AF: 0.435 AC: 19361 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4326 AN: 26062

East Asian (EAS) AF: 0.386 AC: 15293 AN: 39658

South Asian (SAS) AF: 0.270 AC: 23275 AN: 86128

European-Finnish (FIN) AF: 0.220 AC: 11726 AN: 53384

Middle Eastern (MID) AF: 0.315 AC: 1807 AN: 5738

European-Non Finnish (NFE) AF: 0.204 AC: 226992 AN: 1110576

Other (OTH) AF: 0.273 AC: 16474 AN: 60254

GnomAD4 genome AF: 0.390 AC: 59155 AN: 151824 Hom.: 15935 Cov.: 32 AF XY: 0.389 AC XY: 28864 AN XY: 74188

African (AFR) AF: 0.757 AC: 31385 AN: 41438

American (AMR) AF: 0.406 AC: 6186 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2257 AN: 5126

South Asian (SAS) AF: 0.285 AC: 1373 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2390 AN: 10556

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13991 AN: 67874

Other (OTH) AF: 0.379 AC: 799 AN: 2108

Alfa AF: 0.255 Hom.: 22020

Bravo AF: 0.421

TwinsUK AF: 0.186 AC: 688

ALSPAC AF: 0.198 AC: 762

ESP6500AA AF: 0.741 AC: 3266

ESP6500EA AF: 0.204 AC: 1752

ExAC AF: 0.301 AC: 36496

Asia WGS AF: 0.406 AC: 1410 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.15
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.0	.;T
MetaRNN	Benign	0.0000012	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.8	N;N
PhyloP100		3.2
PROVEAN	Benign	3.0	N;.
REVEL	Uncertain	0.30
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Vest4		0.044
ClinPred		0.0063	T
GERP RS		5.8
PromoterAI		0.050	Neutral
Varity_R		0.14
gMVP		0.17
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs8097425; hg19: chr18-61582867; COSMIC: COSV53072921;