rs448940

Positions:

• chr6-25510987-A-G

Variant summary

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

The NM_017640.6(CARMIL1):​c.1632+225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,968 control chromosomes in the GnomAD database, including 14,874 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 0.44 (14874 hom., cov: 32)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.1632+225A>G		intron_variant		ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.1632+225A>G		intron_variant		1	NM_017640.6	ENSP00000331983.6
CARMIL1	ENST00000700669.1	c.1632+225A>G		intron_variant				ENSP00000515137.1
CARMIL1	ENST00000635618.1	n.414+225A>G		intron_variant		5		ENSP00000489114.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66277 AN: 151850 Hom.: 14846 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.436 AC: 66334 AN: 151968 Hom.: 14874 Cov.: 32 AF XY: 0.440 AC XY: 32654 AN XY: 74288

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.444

Alfa AF: 0.428 Hom.: 1727

Bravo AF: 0.434

Asia WGS AF: 0.301 AC: 1049 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.75

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: rs448940; hg19: chr6-25511215;