rs12526480

chr6-25533306-T-G

Variant summary

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

The NM_017640.6(CARMIL1):c.2067+4413T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,990 control chromosomes in the GnomAD database, including 7,917 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 0.32 (7917 hom., cov: 31)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.916

Genes affected

CARMIL1 (HGNC:21581): (capping protein regulator and myosin 1 linker 1) Involved in several processes, including actin filament network formation; plasma membrane bounded cell projection organization; and positive regulation of cellular component organization. Located in several cellular components, including lamellipodium; macropinosome; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARMIL1	NM_017640.6	c.2067+4413T>G		intron_variant		ENST00000329474.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARMIL1	ENST00000329474.7	c.2067+4413T>G		intron_variant		1	NM_017640.6	P1
CARMIL1	ENST00000700669.1	c.2067+4413T>G		intron_variant
CARMIL1	ENST00000635618.1	c.849+4413T>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48457 AN: 151874 Hom.: 7899 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.319 AC: 48523 AN: 151990 Hom.: 7917 Cov.: 31 AF XY: 0.317 AC XY: 23553 AN XY: 74296

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.321

Alfa AF: 0.334 Hom.: 18225

Bravo AF: 0.325

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	8.6
Dann	Benign	0.59

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: rs12526480; hg19: chr6-25533534;