1-46177421-A-G

Variant names:

• chr1-46177421-A-G
• rs7536272
• NM_005727.4:c.-142+2012A>G

Variant summary

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

The NM_005727.4(TSPAN1):​c.-142+2012A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,976 control chromosomes in the GnomAD database, including 4,601 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4601 hom., cov: 31)
• Consequence: TSPAN1 NM_005727.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.53
• Publications: 6 publications found

Genes affected

TSPAN1 (HGNC:20657): (tetraspanin 1) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 1-46177421-A-G is Benign according to our data. Variant chr1-46177421-A-G is described in ClinVar as Benign. ClinVar VariationId is 1281508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005727.4. 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
	TSPAN1	NM_005727.4	MANE Select	c.-142+2012A>G		intron	N/A	NP_005718.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN1	ENST00000372003.6	TSL:1 MANE Select	c.-142+2012A>G		intron	N/A	ENSP00000361072.1	O60635
	TSPAN1	ENST00000893420.1		c.-9+2012A>G		intron	N/A	ENSP00000563479.1
	TSPAN1	ENST00000893421.1		c.-142+2012A>G		intron	N/A	ENSP00000563480.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34425 AN: 151858 Hom.: 4574 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34514 AN: 151976 Hom.: 4601 Cov.: 31 AF XY: 0.235 AC XY: 17425 AN XY: 74282

African (AFR) AF: 0.330 AC: 13672 AN: 41420

American (AMR) AF: 0.245 AC: 3736 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3472

East Asian (EAS) AF: 0.376 AC: 1944 AN: 5168

South Asian (SAS) AF: 0.418 AC: 2017 AN: 4822

European-Finnish (FIN) AF: 0.224 AC: 2358 AN: 10536

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9708 AN: 67992

Other (OTH) AF: 0.210 AC: 443 AN: 2110

Alfa AF: 0.188 Hom.: 414

Bravo AF: 0.230

Asia WGS AF: 0.425 AC: 1476 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	-1.0
CADD	Benign	0.33
DANN	Benign	0.37
PhyloP100		-2.5
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: rs7536272; hg19: chr1-46643093;