rs9327744

Positions:

• chr5-136138073-G-A

Variant summary

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

The NM_005903.7(SMAD5):​c.-245+5111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,196 control chromosomes in the GnomAD database, including 2,297 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 0.17 (2297 hom., cov: 32)
• Consequence: SMAD5 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

Genes affected

SMAD5 (HGNC:6771): (SMAD family member 5) The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.-245+5111G>A		intron_variant		ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.-245+5111G>A		intron_variant		1	NM_005903.7	ENSP00000441954	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26177 AN: 152078 Hom.: 2298 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.172 AC: 26167 AN: 152196 Hom.: 2297 Cov.: 32 AF XY: 0.166 AC XY: 12319 AN XY: 74384

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0965

Gnomad4 SAS AF: 0.0966

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.201

Alfa AF: 0.192 Hom.: 3807

Bravo AF: 0.174

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	18
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: rs9327744; hg19: chr5-135473762;