8-4044980-A-T

Position:

• chr8-4044980-A-T

Variant summary

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

The NM_033225.6(CSMD1):​c.416-12881T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,106 control chromosomes in the GnomAD database, including 5,447 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 0.27 (5447 hom., cov: 34)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.416-12881T>A		intron_variant		ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.416-12881T>A		intron_variant			XP_011533054.1
CSMD1	XM_017013731.2	c.416-12881T>A		intron_variant			XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.416-12881T>A		intron_variant		5	NM_033225.6	ENSP00000489225	P4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40450 AN: 151988 Hom.: 5442 Cov.: 34

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.266 AC: 40490 AN: 152106 Hom.: 5447 Cov.: 34 AF XY: 0.263 AC XY: 19559 AN XY: 74356

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.275

Alfa AF: 0.156 Hom.: 281

Bravo AF: 0.271

Asia WGS AF: 0.230 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.69

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: rs9772485; hg19: chr8-3902502;