rs742132

Variant names:

• chr6-25607343-A-G
• rs742132
• NM_017640.6:c.3847+1070A>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.3847+1070A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,012 control chromosomes in the GnomAD database, including 6,386 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 0.29 (6386 hom., cov: 31)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 53 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.3847+1070A>G		intron_variant	Intron 35 of 36	ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.3847+1070A>G		intron_variant	Intron 35 of 36	1	NM_017640.6	ENSP00000331983.6
CARMIL1	ENST00000700669.1	c.3829+1070A>G		intron_variant	Intron 35 of 36			ENSP00000515137.1
CARMIL1	ENST00000635618.1	n.2647+1070A>G		intron_variant	Intron 22 of 25	5		ENSP00000489114.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43759 AN: 151894 Hom.: 6375 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.288 AC: 43799 AN: 152012 Hom.: 6386 Cov.: 31 AF XY: 0.284 AC XY: 21069 AN XY: 74300

African (AFR) AF: 0.295 AC: 12237 AN: 41434

American (AMR) AF: 0.280 AC: 4281 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3466

East Asian (EAS) AF: 0.260 AC: 1343 AN: 5158

South Asian (SAS) AF: 0.286 AC: 1374 AN: 4812

European-Finnish (FIN) AF: 0.238 AC: 2510 AN: 10560

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20282 AN: 67986

Other (OTH) AF: 0.281 AC: 593 AN: 2112

Alfa AF: 0.297 Hom.: 23394

Bravo AF: 0.293

Asia WGS AF: 0.347 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.73
PhyloP100		-1.0
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: rs742132; hg19: chr6-25607571;