rs1124163

Positions:

• chr6-148480583-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015278.5(SASH1):​c.627+6361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,994 control chromosomes in the GnomAD database, including 2,993 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 0.18 (2993 hom., cov: 31)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

Genes affected

SASH1 (HGNC:19182): (SAM and SH3 domain containing 1) This gene encodes a scaffold protein involved in the TLR4 signaling pathway that may stimulate cytokine production and endothelial cell migration in response to invading pathogens. The encoded protein has also been described as a potential tumor suppressor that may negatively regulate proliferation, apoptosis, and invasion of cancer cells, and reduced expression of this gene has been observed in multiple human cancers. Mutations in this gene may be associated with abnormal skin pigmentation in human patients. [provided by RefSeq, Oct 2016]

CYP51A1P3 (HGNC:41991): (cytochrome P450 family 51 subfamily A member 1 pseudogene 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SASH1	NM_015278.5	c.627+6361C>T		intron_variant		ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SASH1	ENST00000367467.8	c.627+6361C>T		intron_variant		1	NM_015278.5	ENSP00000356437.3
CYP51A1P3	ENST00000400072.3	n.1248C>T		non_coding_transcript_exon_variant	3/3	6
SASH1	ENST00000637469.1	n.71-7031C>T		intron_variant		4		ENSP00000490499.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26888 AN: 151806 Hom.: 2984 Cov.: 31

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.147 AC: 10 AN: 68 Hom.: 0 Cov.: 0 AF XY: 0.132 AC XY: 5 AN XY: 38

Gnomad4 AFR exome AF: 0.333

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.177 AC: 26904 AN: 151926 Hom.: 2993 Cov.: 31 AF XY: 0.176 AC XY: 13086 AN XY: 74256

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.170

Alfa AF: 0.135 Hom.: 818

Bravo AF: 0.180

Asia WGS AF: 0.193 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.57
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1124163; hg19: chr6-148801719; COSMIC: COSV66565223;