NM_001394037.1:c.499-985G>A

Variant names:

• chr15-45179291-C-T
• rs1648307
• NM_001394037.1:c.499-985G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394037.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHF	NM_001394037.1	MANE Select	c.499-985G>A		intron	N/A	NP_001380966.1
	SHF	NM_001301168.2		c.499-985G>A		intron	N/A	NP_001288097.2
	SHF	NM_138356.3		c.304-985G>A		intron	N/A	NP_612365.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHF	ENST00000690270.1	MANE Select	c.499-985G>A		intron	N/A	ENSP00000508579.1
	SHF	ENST00000290894.12	TSL:2	c.304-985G>A		intron	N/A	ENSP00000290894.8
	SHF	ENST00000560471.5	TSL:5	c.499-985G>A		intron	N/A	ENSP00000453260.1

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

African (AFR) AF: 0.134 AC: 5567 AN: 41516

American (AMR) AF: 0.349 AC: 5342 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1512 AN: 3472

East Asian (EAS) AF: 0.0583 AC: 302 AN: 5180

South Asian (SAS) AF: 0.328 AC: 1584 AN: 4830

European-Finnish (FIN) AF: 0.509 AC: 5383 AN: 10570

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37534 AN: 67982

Other (OTH) AF: 0.394 AC: 829 AN: 2104

Alfa AF: 0.429 Hom.: 2448

Bravo AF: 0.364

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.59
PhyloP100		0.016
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: rs1648307; hg19: chr15-45471489; COSMIC: COSV52052909; COSMIC: COSV52052909;