5-136174741-C-G

Variant names:

• chr5-136174741-C-G
• rs10515478
• NM_005903.7:c.1254+109C>G

Variant summary

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

The NM_005903.7(SMAD5):​c.1254+109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 714,996 control chromosomes in the GnomAD database, including 3,941 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 0.095 (824 hom., cov: 32)
  • Exomes 𝑓: 0.092 (3117 hom.)
• Consequence: SMAD5 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.1254+109C>G		intron_variant	Intron 7 of 7	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.1254+109C>G		intron_variant	Intron 7 of 7	1	NM_005903.7	ENSP00000441954.2

Frequencies

GnomAD3 genomes AF: 0.0952 AC: 14455 AN: 151842 Hom.: 824 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0919 AC: 51723 AN: 563036 Hom.: 3117 AF XY: 0.0904 AC XY: 26605 AN XY: 294424

African (AFR) AF: 0.104 AC: 1530 AN: 14714

American (AMR) AF: 0.113 AC: 2858 AN: 25374

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 911 AN: 14692

East Asian (EAS) AF: 0.260 AC: 8776 AN: 33720

South Asian (SAS) AF: 0.0766 AC: 3490 AN: 45574

European-Finnish (FIN) AF: 0.130 AC: 5035 AN: 38722

Middle Eastern (MID) AF: 0.103 AC: 237 AN: 2296

European-Non Finnish (NFE) AF: 0.0730 AC: 26160 AN: 358474

Other (OTH) AF: 0.0925 AC: 2726 AN: 29470

GnomAD4 genome AF: 0.0952 AC: 14473 AN: 151960 Hom.: 824 Cov.: 32 AF XY: 0.0990 AC XY: 7351 AN XY: 74258

African (AFR) AF: 0.101 AC: 4181 AN: 41446

American (AMR) AF: 0.0955 AC: 1457 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1400 AN: 5182

South Asian (SAS) AF: 0.0806 AC: 388 AN: 4812

European-Finnish (FIN) AF: 0.138 AC: 1450 AN: 10516

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0754 AC: 5124 AN: 67966

Other (OTH) AF: 0.106 AC: 223 AN: 2104

Alfa AF: 0.0372 Hom.: 23

Bravo AF: 0.0961

Asia WGS AF: 0.204 AC: 712 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	2.5
DANN	Benign	0.60
PhyloP100		-1.2
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: rs10515478; hg19: chr5-135510430; COSMIC: COSV72597218; COSMIC: COSV72597218;