rs12526480

Variant names:

• chr6-25533306-T-G
• rs12526480
• NM_017640.6:c.2067+4413T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.2067+4413T>G		intron_variant	Intron 24 of 36	ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.2067+4413T>G		intron_variant	Intron 24 of 36	1	NM_017640.6	ENSP00000331983.6
CARMIL1	ENST00000700669.1	c.2067+4413T>G		intron_variant	Intron 24 of 36			ENSP00000515137.1
CARMIL1	ENST00000635618.1	n.849+4413T>G		intron_variant	Intron 10 of 25	5		ENSP00000489114.1

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

African (AFR) AF: 0.311 AC: 12905 AN: 41430

American (AMR) AF: 0.332 AC: 5073 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3466

East Asian (EAS) AF: 0.259 AC: 1337 AN: 5170

South Asian (SAS) AF: 0.353 AC: 1696 AN: 4810

European-Finnish (FIN) AF: 0.271 AC: 2864 AN: 10576

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22758 AN: 67948

Other (OTH) AF: 0.321 AC: 679 AN: 2112

Alfa AF: 0.334 Hom.: 37815

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
PhyloP100		0.92
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: rs12526480; hg19: chr6-25533534;