rs1648307

Positions:

• chr15-45179291-C-T

Variant summary

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

The NM_001394037.1(SHF):​c.499-985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,152 control chromosomes in the GnomAD database, including 14,177 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 0.39 (14177 hom., cov: 33)
• Consequence: SHF NM_001394037.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

Genes affected

SHF (HGNC:25116): (Src homology 2 domain containing F) Predicted to enable phosphotyrosine residue binding activity. Predicted to be involved in apoptotic process. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903481 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHF	NM_001394037.1	c.499-985G>A		intron_variant		ENST00000690270.1	NP_001380966.1
LOC124903481	XR_007064608.1	n.988C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHF	ENST00000690270.1	c.499-985G>A		intron_variant			NM_001394037.1	ENSP00000508579	P1
	ENST00000560034.1	n.191+8757C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58867 AN: 152034 Hom.: 14176 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.387 AC: 58856 AN: 152152 Hom.: 14177 Cov.: 33 AF XY: 0.382 AC XY: 28394 AN XY: 74368

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.394

Alfa AF: 0.439 Hom.: 2443

Bravo AF: 0.364

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.59

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: rs1648307; hg19: chr15-45471489; COSMIC: COSV52052909; COSMIC: COSV52052909;