chr5-136138073-G-A

Variant names:

• chr5-136138073-G-A
• rs9327744
• NM_005903.7:c.-245+5111G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.-245+5111G>A		intron_variant	Intron 1 of 7	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.-245+5111G>A		intron_variant	Intron 1 of 7	1	NM_005903.7	ENSP00000441954.2

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

African (AFR) AF: 0.168 AC: 6990 AN: 41522

American (AMR) AF: 0.137 AC: 2091 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3468

East Asian (EAS) AF: 0.0965 AC: 500 AN: 5184

South Asian (SAS) AF: 0.0966 AC: 466 AN: 4826

European-Finnish (FIN) AF: 0.142 AC: 1502 AN: 10588

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13267 AN: 67998

Other (OTH) AF: 0.201 AC: 424 AN: 2110

Alfa AF: 0.191 Hom.: 4802

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
PhyloP100		1.6
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: rs9327744; hg19: chr5-135473762;