5-17275255-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_006317.5(BASP1):c.39T>C(p.Asn13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,612,252 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (37 hom.)
• Consequence: BASP1 NM_006317.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.863

Genes affected

BASP1 (HGNC:957): (brain abundant membrane attached signal protein 1) This gene encodes a membrane bound protein with several transient phosphorylation sites and PEST motifs. Conservation of proteins with PEST sequences among different species supports their functional significance. PEST sequences typically occur in proteins with high turnover rates. Immunological characteristics of this protein are species specific. This protein also undergoes N-terminal myristoylation. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-17275255-T-C is Benign according to our data. Variant chr5-17275255-T-C is described in ClinVar as [Benign]. Clinvar id is 788981.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.863 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1785/151616) while in subpopulation AFR AF= 0.0411 (1698/41362). AF 95% confidence interval is 0.0394. There are 33 homozygotes in gnomad4. There are 829 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BASP1	NM_006317.5	c.39T>C	p.Asn13=	synonymous_variant	2/2	ENST00000322611.4
BASP1	NM_001271606.2	c.39T>C	p.Asn13=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BASP1	ENST00000322611.4	c.39T>C	p.Asn13=	synonymous_variant	2/2	1	NM_006317.5	P1
BASP1	ENST00000616743.1	c.39T>C	p.Asn13=	synonymous_variant	2/2	3		P1
BASP1	ENST00000606445.1	c.39T>C	p.Asn13=	synonymous_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1779 AN: 151498 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00440

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00313 AC: 778 AN: 248742 Hom.: 17 AF XY: 0.00218 AC XY: 294 AN XY: 135170

Gnomad AFR exome AF: 0.0434

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000983

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.000984

GnomAD4 exome AF: 0.00119 AC: 1741 AN: 1460636 Hom.: 37 Cov.: 32 AF XY: 0.000999 AC XY: 726 AN XY: 726732

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.00246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000342

Gnomad4 OTH exome AF: 0.00313

GnomAD4 genome AF: 0.0118 AC: 1785 AN: 151616 Hom.: 33 Cov.: 32 AF XY: 0.0112 AC XY: 829 AN XY: 74080

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.00440

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00598 Hom.: 3

Bravo AF: 0.0134

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	4.3
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs73756114; hg19: chr5-17275364;