rs10456324

Variant names:

• chr6-25600740-G-A
• rs10456324
• NM_017640.6:c.3546G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-25600740-G-A
• chr6-25600740-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017640.6(CARMIL1):​c.3546G>A​(p.Ala1182Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,518,214 control chromosomes in the GnomAD database, including 145,253 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 0.41 (13250 hom., cov: 32)
  • Exomes 𝑓: 0.44 (132003 hom.)
• Consequence: CARMIL1 NM_017640.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 19 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017640.6. 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
	CARMIL1	NM_017640.6	MANE Select	c.3546G>A	p.Ala1182Ala	synonymous	Exon 33 of 37	NP_060110.4
	CARMIL1	NM_001173977.2		c.3546G>A	p.Ala1182Ala	synonymous	Exon 33 of 37	NP_001167448.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL1	ENST00000329474.7	TSL:1 MANE Select	c.3546G>A	p.Ala1182Ala	synonymous	Exon 33 of 37	ENSP00000331983.6
	CARMIL1	ENST00000700669.1		c.3546G>A	p.Ala1182Ala	synonymous	Exon 33 of 37	ENSP00000515137.1
	CARMIL1	ENST00000635618.1	TSL:5	n.2346G>A		non_coding_transcript_exon	Exon 20 of 26	ENSP00000489114.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62772 AN: 151862 Hom.: 13241 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.399

GnomAD2 exomes AF: 0.434 AC: 69361 AN: 159654 AF XY: 0.439

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.402

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.374

Gnomad FIN exome AF: 0.408

Gnomad NFE exome AF: 0.463

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.438 AC: 598105 AN: 1366232 Hom.: 132003 Cov.: 36 AF XY: 0.439 AC XY: 294459 AN XY: 670360

African (AFR) AF: 0.349 AC: 10545 AN: 30220

American (AMR) AF: 0.395 AC: 11024 AN: 27896

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 9249 AN: 20800

East Asian (EAS) AF: 0.335 AC: 12813 AN: 38228

South Asian (SAS) AF: 0.445 AC: 31293 AN: 70246

European-Finnish (FIN) AF: 0.406 AC: 20176 AN: 49714

Middle Eastern (MID) AF: 0.462 AC: 2470 AN: 5348

European-Non Finnish (NFE) AF: 0.446 AC: 476084 AN: 1067426

Other (OTH) AF: 0.434 AC: 24451 AN: 56354

GnomAD4 genome AF: 0.413 AC: 62815 AN: 151982 Hom.: 13250 Cov.: 32 AF XY: 0.410 AC XY: 30435 AN XY: 74290

African (AFR) AF: 0.353 AC: 14628 AN: 41438

American (AMR) AF: 0.394 AC: 6024 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1916 AN: 5150

South Asian (SAS) AF: 0.454 AC: 2187 AN: 4818

European-Finnish (FIN) AF: 0.392 AC: 4145 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30948 AN: 67930

Other (OTH) AF: 0.404 AC: 854 AN: 2112

Alfa AF: 0.442 Hom.: 61215

Bravo AF: 0.411

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.37
DANN	Benign	0.33
PhyloP100		-1.6
Mutation Taster		=98/2	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: rs10456324; hg19: chr6-25600968; COSMIC: COSV61516324;