rs11781525

Variant names:

• chr8-124709125-G-A
• rs11781525
• NM_014751.6:c.73-4934C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000518547.6(MTSS1):​c.73-4934C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 152,194 control chromosomes in the GnomAD database, including 117 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 0.030 (117 hom., cov: 32)
• Consequence: MTSS1 ENST00000518547.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 6 publications found

Genes affected

MTSS1 (HGNC:20443): (MTSS I-BAR domain containing 1) Enables actin monomer binding activity; identical protein binding activity; and signaling receptor binding activity. Predicted to be involved in cellular response to fluid shear stress; negative regulation of epithelial cell proliferation; and urogenital system development. Predicted to act upstream of or within several processes, including actin filament polymerization; adherens junction maintenance; and magnesium ion homeostasis. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0304 (4627/152194) while in subpopulation NFE AF = 0.0437 (2974/68010). AF 95% confidence interval is 0.0424. There are 117 homozygotes in GnomAd4. There are 2341 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4627 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518547.6. 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
	MTSS1	NM_014751.6	MANE Select	c.73-4934C>T		intron	N/A	NP_055566.3
	MTSS1	NM_001282971.2		c.73-4934C>T		intron	N/A	NP_001269900.1
	MTSS1	NM_001363294.2		c.73-4934C>T		intron	N/A	NP_001350223.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTSS1	ENST00000518547.6	TSL:1 MANE Select	c.73-4934C>T		intron	N/A	ENSP00000429064.1
	MTSS1	ENST00000378017.7	TSL:1	c.73-4934C>T		intron	N/A	ENSP00000367256.3
	MTSS1	ENST00000325064.9	TSL:2	c.73-4934C>T		intron	N/A	ENSP00000322804.5

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4626 AN: 152076 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.00790

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0304 AC: 4627 AN: 152194 Hom.: 117 Cov.: 32 AF XY: 0.0315 AC XY: 2341 AN XY: 74394

African (AFR) AF: 0.00790 AC: 328 AN: 41536

American (AMR) AF: 0.0176 AC: 269 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00747 AC: 36 AN: 4822

European-Finnish (FIN) AF: 0.0837 AC: 885 AN: 10570

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0437 AC: 2974 AN: 68010

Other (OTH) AF: 0.0246 AC: 52 AN: 2112

Alfa AF: 0.0262 Hom.: 24

Bravo AF: 0.0250

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.58
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

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: rs11781525; hg19: chr8-125721366;