rs1944269

Variant names:

• chr18-63980032-C-T
• rs1944269
• NM_002640.4:c.306+94C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-63980032-C-T
• chr18-63980032-C-A
• chr18-63980032-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002640.4(SERPINB8):​c.306+94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,263,838 control chromosomes in the GnomAD database, including 296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (170 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (126 hom.)
• Consequence: SERPINB8 NM_002640.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0730
• Publications: 0 publications found

Genes affected

SERPINB8 (HGNC:8952): (serpin family B member 8) The protein encoded by this gene is a member of the ov-serpin family of serine protease inhibitors. The encoded protein is produced by platelets and can bind to and inhibit the function of furin, a serine protease involved in platelet functions. In addition, this protein has been found to enhance the mechanical stability of cell-cell adhesion in the skin, and defects in this gene have been associated with an autosomal-recessive form of exfoliative ichthyosis. [provided by RefSeq, Jan 2017]

HMSD (HGNC:23037): (histocompatibility minor serpin domain containing) This gene encodes a serpin-domain containing protein that may function as a serine protease inhibitor. This gene is primarily expressed in cells of myeloid lineage. A polymorphism in this gene may result in the expression a splice variant that encodes a minor histocompatibility antigen. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-63980032-C-T is Benign according to our data. Variant chr18-63980032-C-T is described in ClinVar as Benign. ClinVar VariationId is 1178309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002640.4. 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
	SERPINB8	NM_002640.4	MANE Select	c.306+94C>T		intron	N/A	NP_002631.3
	SERPINB8	NM_001366198.1		c.306+94C>T		intron	N/A	NP_001353127.1	P50452-1
	SERPINB8	NM_198833.2		c.306+94C>T		intron	N/A	NP_942130.1	P50452-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB8	ENST00000397985.7	TSL:1 MANE Select	c.306+94C>T		intron	N/A	ENSP00000381072.2	P50452-1
	SERPINB8	ENST00000397988.7	TSL:1	c.306+94C>T		intron	N/A	ENSP00000381075.3	P50452-2
	SERPINB8	ENST00000353706.6	TSL:5	c.306+94C>T		intron	N/A	ENSP00000331368.3	P50452-1

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4081 AN: 152152 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0933

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.00267 AC: 2972 AN: 1111568 Hom.: 126 AF XY: 0.00226 AC XY: 1265 AN XY: 559150

African (AFR) AF: 0.0971 AC: 2436 AN: 25096

American (AMR) AF: 0.00421 AC: 141 AN: 33496

Ashkenazi Jewish (ASJ) AF: 0.0000480 AC: 1 AN: 20852

East Asian (EAS) AF: 0.00 AC: 0 AN: 37082

South Asian (SAS) AF: 0.000143 AC: 10 AN: 69960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45298

Middle Eastern (MID) AF: 0.00203 AC: 8 AN: 3938

European-Non Finnish (NFE) AF: 0.000112 AC: 93 AN: 828000

Other (OTH) AF: 0.00591 AC: 283 AN: 47846

GnomAD4 genome AF: 0.0269 AC: 4096 AN: 152270 Hom.: 170 Cov.: 32 AF XY: 0.0261 AC XY: 1947 AN XY: 74466

African (AFR) AF: 0.0934 AC: 3879 AN: 41536

American (AMR) AF: 0.0103 AC: 157 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68022

Other (OTH) AF: 0.0180 AC: 38 AN: 2110

Alfa AF: 0.00430 Hom.: 1

Bravo AF: 0.0311

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.55
PhyloP100		-0.073
PromoterAI		-0.0042	Neutral
Mutation Taster		=100/0	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: rs1944269; hg19: chr18-61647266;