6-70747350-A-C

Variant names:

• chr6-70747350-A-C
• rs10498874
• NM_001044305.3:c.253-7630A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001044305.3(SMAP1):​c.253-7630A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,058 control chromosomes in the GnomAD database, including 14,742 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 0.43 (14742 hom., cov: 32)
• Consequence: SMAP1 NM_001044305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 12 publications found

Genes affected

SMAP1 (HGNC:19651): (small ArfGAP 1) The protein encoded by this gene is similar to the mouse stromal membrane-associated protein-1. This similarity suggests that this human gene product is also a type II membrane glycoprotein involved in the erythropoietic stimulatory activity of stromal cells. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3	c.253-7630A>C		intron_variant	Intron 2 of 10	ENST00000370455.8	NP_001037770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAP1	ENST00000370455.8	c.253-7630A>C		intron_variant	Intron 2 of 10	1	NM_001044305.3	ENSP00000359484.3
SMAP1	ENST00000619054.4	c.223-7630A>C		intron_variant	Intron 2 of 10	1		ENSP00000484538.1
SMAP1	ENST00000316999.9	c.253-7630A>C		intron_variant	Intron 2 of 9	1		ENSP00000313382.5
SMAP1	ENST00000370452.7	c.253-7630A>C		intron_variant	Intron 2 of 10	2		ENSP00000359481.3

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66090 AN: 151940 Hom.: 14743 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.435 AC: 66102 AN: 152058 Hom.: 14742 Cov.: 32 AF XY: 0.433 AC XY: 32168 AN XY: 74324

African (AFR) AF: 0.377 AC: 15639 AN: 41478

American (AMR) AF: 0.421 AC: 6418 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1202 AN: 5170

South Asian (SAS) AF: 0.497 AC: 2394 AN: 4816

European-Finnish (FIN) AF: 0.445 AC: 4699 AN: 10558

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32810 AN: 67990

Other (OTH) AF: 0.457 AC: 963 AN: 2108

Alfa AF: 0.462 Hom.: 52634

Bravo AF: 0.425

Asia WGS AF: 0.374 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.4
DANN	Benign	0.69
PhyloP100		0.23
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: rs10498874; hg19: chr6-71457053;