rs6032474

Variant names:

• chr20-45725733-G-A
• rs6032474
• NM_178455.3:c.*98G>A

Variant summary

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

The NM_178455.3(SPINT4):​c.*98G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,481,854 control chromosomes in the GnomAD database, including 124,947 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.

• Frequency:
  • Genomes: 𝑓 0.46 (17977 hom., cov: 32)
  • Exomes 𝑓: 0.39 (106970 hom.)
• Consequence: SPINT4 NM_178455.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 15 publications found

Genes affected

SPINT4 (HGNC:16130): (serine peptidase inhibitor, Kunitz type 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178455.3. 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
	SPINT4	NM_178455.3	MANE Select	c.*98G>A		3_prime_UTR	Exon 3 of 3	NP_848550.1	Q6UDR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINT4	ENST00000279058.4	TSL:1 MANE Select	c.*98G>A		3_prime_UTR	Exon 3 of 3	ENSP00000279058.3	Q6UDR6

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70394 AN: 151792 Hom.: 17955 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.391 AC: 519537 AN: 1329944 Hom.: 106970 Cov.: 19 AF XY: 0.396 AC XY: 264642 AN XY: 667456

African (AFR) AF: 0.686 AC: 21228 AN: 30954

American (AMR) AF: 0.291 AC: 12782 AN: 43900

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 13857 AN: 25274

East Asian (EAS) AF: 0.461 AC: 17982 AN: 39030

South Asian (SAS) AF: 0.547 AC: 45393 AN: 82988

European-Finnish (FIN) AF: 0.386 AC: 20398 AN: 52810

Middle Eastern (MID) AF: 0.527 AC: 2922 AN: 5544

European-Non Finnish (NFE) AF: 0.363 AC: 360855 AN: 993454

Other (OTH) AF: 0.431 AC: 24120 AN: 55990

GnomAD4 genome AF: 0.464 AC: 70454 AN: 151910 Hom.: 17977 Cov.: 32 AF XY: 0.465 AC XY: 34522 AN XY: 74232

African (AFR) AF: 0.673 AC: 27907 AN: 41458

American (AMR) AF: 0.347 AC: 5296 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2532 AN: 5174

South Asian (SAS) AF: 0.546 AC: 2628 AN: 4812

European-Finnish (FIN) AF: 0.391 AC: 4120 AN: 10526

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24755 AN: 67902

Other (OTH) AF: 0.469 AC: 989 AN: 2108

Alfa AF: 0.410 Hom.: 39829

Bravo AF: 0.468

Asia WGS AF: 0.493 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.31
PhyloP100		-0.16
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: rs6032474; hg19: chr20-44354372; COSMIC: COSV54143276;